In vitro assays were used to determine if organophosphate, carbamate, and synthetic pyrethroid insecticides affected the cytochrome P450 monooxygenase (P450) catalyzed hydroxylation of nicosulfuron, bentazon, cinnamic acid, or lauric acid in maize microsomes. All P450 activities were inhibited approximately 50% by carbaryl, and none were inhibited by permethrin. Hydroxylations of nicosulfuron, bentazon, lauric acid, and cinnamic acid were inhibited by malathion 83, 92, 38, and 0%, respectively. Terbufos was only moderately (36%) inhibitory of in vitro P450 hydroxylation of nicosulfuron. Nicosulfuron hydroxylation was more sensitive than bentazon hydroxylation to inhibition by the insecticides, and both herbicide hydroxylations were more sensitive than lauric acid or cinnamic acid hydroxylations to the insecticides. Since the oxidative metabolites of terbufos were shown to be more potent inhibitors of in vivo nicosulfuron metabolism than terbufos, we examined the effect of terbufos-sulfone on in vivo and in vitro herbicide metabolism. Terbufos-sulfone inhibited metabolism of nicosulfuron and imazethapyr, but not bentazon, in excised corn shoots. Microsomal hydroxylation of nicosulfuron, bentazon, chlorimuron ethyl, and imazethapyr, as well as the desulfuration of malathion, were strongly inhibited (>65%) by terbufos-sulfone. Cinnamic acid hydroxylase appeared to be different from the P450(s) responsible for the pesticide metabolism as it was not inhibited by terbufos-sulfone. However, the data also suggest that malathion, nicosulfuron, bentazon, chlorimuron ethyl, and imazethapyr all share a P450 in common with terbufos-sulfone. Alternatively, there may be separate P450s for the metabolism of the herbicides and malathion, all of which also metabolize terbufos-sulfone. These data show that the inhibition of P450 hydroxylation of nicosulfuron by terbufos-sulfone can explain the injury when maize is exposed to both terbufos and nicosulfuron. However, the insecticides that are the most potent in vitro P450 inhibitors are not necessarily the ones that cause the most herbicide injury in the field.