Lang et al. express concerns regarding the ecological risk assessment (ERA) approach that we refer to in our Perspective1. They have not addressed the focus of our paper. The real value of our article is the analysis of the studies that have addressed the impact of Bt-transgenic crops on natural enemies and the conclusions drawn for improving future studies for nontarget risk assessment of transgenic plants. In the following, we respond to the three points they raise.Their first point is that acute exposure testing is not sufficient. We never stated that risk assessment studies in the laboratory are restricted to short-term (acute) exposure testing. For a meaningful risk assessment study, measurement endpoints need to be identified that reflect the endpoints of the risk assessment (e.g., populations of nontarget organisms). The design of a study furthermore depends on the known mode of action of the insecticidal protein and the known routes and level of exposure2. The decision tree we propose in our paper (Fig. 1 in ref. 1) is not a risk assessment for laboratory studies. It is a guide for experimenters to perform meaningful studies that can be well interpreted.In their second point, Lang et al. highlight the need for region-specific tests. We fully agree that a nontarget risk assessment needs to take the receiving environment into account2. It is unclear, however, what Lang et al. mean by 'region-specific tests' and how they would conduct such tests (in the laboratory or in the field). There is evidence that Cry1Ab toxin in Bt maize pollen or anthers is a hazard to some larvae of nontarget butterflies; however, hazard does not automatically equate to risk, unless exposure also is demonstrated. For many species, it may be sufficient to assess risk by focusing on exposure. Such an assessment would entail evaluating the potential temporal and spatial overlap of larval stages with maize flowering. This is especially important for many protected or red-list species where no information about the sensitivity toward the Bt toxin is available and cannot be generated3.Their last point strongly advocates that the ERA of transgenic crops should always include field tests. They base this request on two main assumptions: first, field assessment is necessary to address indirect effects of the transgenic crop; and second, results from laboratory studies will never conclude that a transgenic crop poses no risk for nontarget organisms in the field.With respect to indirect effects, such as those due to the transformation process, Lang et al. ignore the fact that all transgenic plants will be assessed as to their familiarity and substantial equivalence compared with their nontransformed near isolines and with commercial crop varieties before commercialization. This includes a detailed characterization of the plant under field conditions. On the basis of this detailed assessment, risk assessors will define the potential stressors that need to be addressed in the ERA4. If the transgenic plant does not differ from its near isoline, the stressor that needs to be assessed is simply the introduced trait (e.g., the expressed Cry protein) and not the whole plant. In cases where substantial differences are detected, these characters become additional stressors that also need to be evaluated.By rejecting the principle that a risk conclusion can be drawn after an assessment in the laboratory, Lang et al. oppose the step-wise (tiered) risk assessment approach that is generally applied for other environmental stressors, including plant protection products5, 6, 7. Early-tier studies, typically (but not always) performed in the laboratory, are conducted to determine whether the stressor poses a hazard for nontarget organisms at elevated doses. Only in cases where a hazard has been detected (and the degree of risk or uncertainty is deemed unacceptable), does the risk assessment proceed to more realistic hazard and exposure scenarios. This approach does include semi-field or field experiments whenever they add certainty to the risk assessment. If early-tier studies show the absence of a hazard with high enough certainty, however, the assessment can be terminated. The fact that Lang et al. request field studies 'regardless of early-tier [laboratory] results' shows that they have no confidence in laboratory studies. If this is the case, then such studies should not be conducted because they are of little use for a risk assessment. In our Perspective, we propose ways to increase the quality of laboratory studies and the interpretability of the data (see the four questions laid out in Fig. 1 in ref. 1).Lang et al. refer to the Monarch butterfly case study to show the shortcomings of laboratory risk assessment studies. In contrast to their interpretation, we are convinced that the Monarch case provides an excellent example on how the tiered risk assessment works when a hazard has been detected. Because toxicological studies have established sensitivity of Monarch larvae to the Cry1Ab protein in Bt maize, higher-tier risk assessment studies were triggered to assess exposure and population level effects8, 9, 10, 11. Similarly, if Cry1Ab containing pollen appears to affect larvae of the Hungarian Peacock butterfly, as stated by Lang et al., more comprehensive assessment (and perhaps testing) will be needed and, depending on the degree and nature of concern, this may extend to field testing. We are of the opinion, however, that an a priori rejection of laboratory findings and uniform institution of field testing-as described by Lang et al.-is neither objective nor consistent with well-recognized approaches to risk assessment. Because results of the Peacock butterfly studies are not published, we are not able to evaluate this case. Similarly, the Scientific Panel on Genetically Modified Organisms of the European Food Safety Authority has recently discounted these reports because they do not contain scientific data 'which can be subjected to detailed scientific scrutiny'12.Because of the impact of several confounding factors, large variability is generally found within treatments in field testing. The fact that these interfering factors can mask potential effects by the stressor (the Cry protein) has been referred to by Ludy and Lang13 as one possible factor to explain why a three-year, field-scale monitoring project did not reveal any effects of Bt maize on foliage-dwelling spiders. The consideration of field studies as preferable to laboratory studies is therefore untenable. Furthermore, the conduct of field studies without first establishing the scope and nature of concern through laboratory studies (which is accommodated under tiered regimes) is not a sound way to either conduct science or risk assessment.The risk assessment approach that we described briefly in our Perspective in no respect aims to 'simplify ERA for reasons of convenient administration or management procedure' by 'simplifying and even ignoring existing, relevant biological knowledge.' Thorough knowledge of certain biological and ecological features of a nontarget organism is a prerequisite to conduct a meaningful and robust tiered risk assessment. Information that would be 'nice to know' about all possible interactions between a nontarget organism, its host plant(s) and external impacts cannot be allowed to supplant the 'need to know' parameters of practical regulatory risk assessment.