Studies are presented on the effects of two synergists, piperonyl butoxide and S,S,S-tributyl phosphorotrithioate, on the metabolism of methoprene [isopropyl (2E,4E)-11-methoxy-3,7,11-trimethyldodeca-2,4-dienoate], an insect growth regulator, by the castes of the imported fire ant, Solenopsis invicta Buren. In adults, but not in larvae, pharate pupae, and pupae, piperonyl butoxide, a microsomal enzyme inhibitor, reduced methoprene metabolism by blocking O-demethylation. S,S,S-Tributyl phosphorotrithioate, an esterase and microsomal oxidase inhibitor, was most effective in reducing methoprene metabolism in larvae. In toxicity studies, against pharate pupae, the O-demethylated methoprene metabolite (alcohol-ester) was shown to be more toxic than methoprene. Synergists may be useful in bait formulations used for imported fire ant control to extend the effectiveness of methoprene. © 1979.