A modified Vip3C protein has been developed that has a spectrum of activity that has the potential to be commercially useful for pest control, and shows good efficacy against Spodoptera frugiperda in insect bioassays and field trials. For the first time Vip3A and Vip3C proteins have been compared to Cry1 and Cry2 proteins in a complete set of experiments from insect bioassays to competition binding assays to field trials, and the results of these complementary experiments are in agreement with each other. Binding assays with radiolabelled toxins and brush border membrane vesicles from S. frugiperda and Helicoverpa armigera show that the modified Vip3C protein shares binding sites with Vip3A, and does not share sites with Cry1F or Cry2A. In agreement with the resulting binding site model, Vip3A-resistant insects were also cross-resistant to the modified Vip3C protein. Furthermore, maize plants expressing the modified Vip3C protein, but not those expressing Cry1F protein, were protected against Cry1F-resistant S. frugiperda in field trials.