Activities of cytochrome P-450-dependent microsomal monooxygenases (PMSO) are up to 46-fold higher in insecticide-susceptible fifth instar tobacco budworm larvae than in adult boll weevils. Glutathione transferase and esterase activities are likewise higher in susceptible tobacco budworm larvae than in adult boll weevils, the life stages of the two species that are exposed to selection pressure from insecticide treatments. Good metabolic defenses may facilitate insecticide resistance development in the tobacco budworm. Differences in ecological, biological, and other biochemical factors, not quantified in this study, are also likely to contribute to the observed differences in resistance development in the two species. PSMO activities as well as glutathione transferase and esterase activities are 3- to 11-fold higher in boll weevil larvae than in adults. Exposure of the life stage with the weakest metabolic defenses to insecticide selection pressure in the boll weevil may contribute to its relative lack of resistance development.