The Federal Insecticide, Fungicide and Rodenticide Act directs the U.S. EPA to examine all potentially adverse environmental impacts, including those which may arise from gene flow of plant-incorporated protectants (PIPs) to wild or feral populations of sexually compatible plants. In addition to this mandate, the Federal Food Drug and Cosmetic Act requires the issuance  of a food tolerance or exemption from the requirement of a tolerance for all pesticidal substances that may enter the food supply whether through seed mixing or cross pollination. To date, three crop species have been registered by the Agency as PIPs and all have received exemptions from the requirement of a tolerance. Maize, cotton and potato were reviewed for their potential to hybridize with wild and feral relatives of sexually compatible plants in the U.S., its territories and possessions. For Zea mays ssp. mays it was concluded that there was no biologically plausible avenue for gene flow to other plants within these geographical boundaries since there are no sexually compatible species present, other than in special plantings ( e.g., herbaria, research plots, demonstration plots). The conclusion for Bt-potato ( Solanum tuberosum ssp. tuberosum) was largely the same since the only compatible relatives are found at higher elevations in the southwest and are not found in areas where commercial potato production occurs. Upland cotton, Gossypium hirsutum, does have the potential to hybridize with Hawaiian cotton, G. tomentosum, and feral populations of G. hirsutum in the Florida Keys, and of G. hirsutum / G. barbadense on the U.S. Virgin Islands and Puerto Rico. For these reasons, restrictions on field plot experimental use permits and commercial planting of Bt-cotton has been instituted in these areas.