Evidence supporting the view of an active role of free fatty acids in the pathogenesis of acne consists of (1) the irritating activity of free fatty acids, (2) their comedogenic activity, and (3) the fall in free fatty acid levels on the skin during tetracycline therapy. Evidence that free fatty acid concentrations in the follicle may be so high as to affect the follicular epithelium is lacking. The bacteria responsible for lipolysis in the follicle produce enzymes other than lipases, as well as antigens and possibly other undefined materials that may play active roles in the production of the acne lesion. The hypothesis that free fatty acids are involved in pathogenesis is, a hypothesis of a microbial pathogenesis of acne; if this is to be considered seriously, facets other than the production of lipases cannot be ignored.