In the presence of NADPH and under aerobic conditions, thioether-containing organo-phosphorus and carbamate pesticides were oxidized by the FAD-dependent monooxygenase (EC 220.127.116.11) purified from pig liver microsomes. The stoichiometric relationship between NADPH and substrate during the course of the reaction was 1:1, and the product, in the case of disulfoton and phorate, was the sulfoxide. The product was optically active and further oxidation to the sulfone was not apparent. Furthermore, the sulfoxides of disulfoton, phorate and croneton were not substrates for this enzyme. n-Octylamine, a known cytochrome P-450 inhibitor, increased the rate of sulfoxidation reactions catalyzed by the FAD-dependent monooxygenase. Structure-activity relationships were investigated using thirty-nine possible substrates. Structural changes around the thioether sulfur that affect nucleophilicity or that cause steric hindrance tended to decrease the sulfoxidation rats. With phosphorodithioates, changes around the phosphorus atom also affected oxidation of the thioether sulfur. Although neither the thiono nor the thiol sulfur atoms were attacked, substitution of either sulfur by oxygen decreased sulfoxidation. Thioether-containing O, O-dimethyl phosphorodithioates were not oxidized as readily as their O, O-diethyl analogs. Tetram and its analogs, which contain a teritiary amine group, were also substrates for this enzyme, presumably forming the N-oxide.