When cat fleas, Ctenocephalides felis (Bouché), were fed concentrations of lufenuron in cattle blood ranging from 0.5 to 4 ppm, adult mortality increased in a dose-dependent manner to a maximum of approximately 24% over a period of 10 d. Fleas treated with 0.5 ppm produced abnormal endocuticle consisting of protein globules embedded in an amorphous chitin matrix. At concentrations of 1.0 ppm or greater, endocuticle formation was inhibited. Ultrastructural studies demonstrated that inhibition of chitin synthesis was associated with degeneration of the epidermal cells. The amount of epidermal cytoplasm decreased and cytoplasmic organelles including mitochondria, ribosomes, and golgi showed lytic changes. At least some mortality of treated fleas was likely the result of a weakened endocuticle and the corresponding decrease in resiliency of the cuticle to expansion during blood-feeding and egg production. An unexpected result of lufenuron treatment was the inhibition of midgut epithelial cell differentiation. At concentrations of 0.5 and 1.0 ppm, partially differentiated epithelial cells were seen in the midgut of bloodfed fleas along with fully differentiated cells.