Extensive field tests with insect resistant cotton plants, which express a Bacillus thuringiensis variety kurstaki protein, have established commercially acceptable levels of control of the targeted lepidopteran insects. These plants have the potential to provide the agricultural community with an effective and environmentally friendly method to control the major insect pests of cotton. The insect resistance trait has been backcrossed into commercial germplasms to produce cotton varieties which combine the best agronomic traits with resistance to lepidopteran insects. As these commercial varieties are being developed and extensively field tested, data have been generated to establish the environmental, animal feed and human food safety of this product. This manuscript summarizes our approach to establish the safety of these insect. resistant cotton plants and to gain regulatory approval for commercialization. We have characterized these plants, genetically, molecularly and biochemically, and established the safety of both the introduced proteins and the products generated from these plants. The introduced proteins have been purified and shown not to cause any adverse effects to non-target organisms when exposed to extremely high doses. These proteins are produced at low levels in the plants and were shown to degrade rapidly during mammalian digestion as well as in the soil. No adverse effects were observed in feeding the cottonseed producing these proteins to rodents, birds or fish. The quality of the seed and oil generated from the seed as well as the level of anti-nutritional components were not significantly altered in these insect resistant plants relative to the non-modified parental variety. We are confident that our broad science-based approach to establish the food, feed and environmental safety of these plants and plant products provides the information necessary to gain regulatory approval and consumer acceptance of this product. Likewise, similar information is being generated to establish the safety of other products that will follow insect resistant cotton into the market place.