This study shows that a diet including insect-resistant Bt176 maize, fed to 53 ewes and their progeny for 3 years, did not have adverse effects on their health or performance and that no horizontal gene transfer to ruminal microorganisms or animal tissues was detected.  No differences were observed regarding performance, reproductive traits, haematological parameters, antioxidant defences, lymphocyte proliferative capacity, phagocytosis and intracellular killing of macrophages, and ruminal microbial population characteristics between control and genetically modified (GM) maize-fed animals.  Immune response to Salmonella abortus ovis vaccination was more efficient in GM maize fed sheep.  No modifications of histological features of tissues were found; however, cytochemical analyses of ruminal epithelium by Ki67 staining provided evidence of proliferative activation of basal cells in all GM maize-fed ewes.  Preliminary electron microscopy analyses of the liver and pancreas revealed smaller cell nuclei containing increased amounts of heterochromatin and perichromatin granules in GM maize-fed lambs.  Meat protein content and water loss by cooking were slightly affected by the dietary treatment.  No transgenic DNA was detected in tissues, blood, and ruminal fluid or ruminal bacteria.  Longitudinal studies should be included in evaluation of food safety whenever possible and sheep may be a useful animal model for toxicological assessment.