Juvenile hormone III plays a major role in regulating feeding and reproduction in the adult cat flea, Ctenocephalides felis (Bouché). Both blood consumption and egg production increased in a dose-dependent manner up to a maximum at 1,250 ppm when fleas were continuously exposed to concentrations up to 12,500 ppm juvenile hormone. Histological studies demonstrated that juvenile hormone III also stimulated cellular differentiation of salivary gland epithelia, midgut epithelia, and fat body cells, enhancing the ability of the adult flea to digest blood and synthesize vitellogenins for the maturing oocytes. In unfed fleas, exposure of adults to concentrations of ≥1,000 ppm juvenile hormone III applied to filter paper resulted in membrane lysis and destruction of salivary gland and midgut epithelial cells, fat body cells, and ovarian tissue. Unlike juvenile hormone mimics, which have potent ovicidal effects in fleas, juvenile hormone had little effect in preventing egg hatch; 58% of the eggs laid by fleas treated with 12,500 ppm juvenile hormone III hatched, and a concentration of 30,000 ppm was required to reduce hatch to 2% in untreated eggs exposed to treated filter paper for 2 h. Compared with the juvenile homone mimic pyriproxyfen, juvenile hormone III was less toxic to fed adult fleas. However, at a concentration of 12,500 ppm, juvenile hormone killed ≈45% of the adults and caused autolysis and yolk resorption in the developing oocytes. Thus, at high concentrations, juvenile hormone appears to have a pharmacological effect on fleas, which is highly unusual in insects.