Our goal to improve the treatment of acne vulgaris has been partially fulfilled. The approach has been to delineate the role of the lipases of the sebaceous follicles in the pathogenesis of this disease. This involved the purification and characterization of the extracellular lipases of Corynebacterium acnes and Staphylococcus epidermidis. Our initial studies indicated that the lipase from C. acnes is inhibited by organophosphates. The in vitro screening of these inhibitors has been partially completed. It was discovered through a collaborative effort with Dow Chemical Co., that halopyridyl phosphorous compounds are potent inhibitors of these extracellular lipases. The compounds have high potency in lipase inhibition coupled with relatively low mammalian toxicity, and are thus well suited for topical use in treatment of acne. Phase I and II clinical studies are now in progress.