Resistance to the spore-crystal protein complex of Bacillus thuringiensis, the most widely used and intensively studied microbial insecticide, has been presumed to be unlikely to occur. In this study it was found that Plodia interpunctella, a major lepidopteran pest of stored grain products, can develop resistance to the insecticide within a few generations. Resistance increased nearly 30-fold in two generations in a strain reared on diet treated with Bacillus thuringiensis and after 15 generations reached a plateau 100 times higher than the control level. Resistance was stable when selection was discontinued. The resistance was inherited as a recessive trait. Plodia interpunctella strains collected from treated grain bins were more resistant than strains from untreated bins, indicating that the resistance can develop quickly in the field.