Among the factors that control the survival of microorganisms on human stratum corneum are skin lipids, including sphingosines. Because the antibacterial spectrum of sphinganine resembles that of cell wall antibiotics, electron microscopy of sphinganine-treated and untreated S. aureus was performed; the lipid induced multiple lesions of cell wall, membrane evaginations and loss of ribosomes. However, comparisons of minimal inhibitory concentration of sphinganine for coccal forms and L-forms of S. aureus, which lack cell walls, and of the respective dose-related reductions in colony-forming units demonstrated both the susceptibility of L-forms and their superior resistance. Therefore, cell wall lesions are sequelae of a probable membrane reaction. Candida albicans was susceptible to sphinganine, sphingosine, dimethylsphingosine, and to a lesser degree, stearylamine. Liquid assays of these lipids against Trichophyton mentagrophytes, T. tonsurans and Epidermatophyton floccosum established their high susceptibility to sphingosine and stearylamine. Sphinganine was the least effective, perhaps due to the presence of L isomers; T. tonsurans was the most sensitive. These four lipids were found to be fungistatic, preventing germination and retarding thalli. Antifungal efficacy was confirmed in vitro on stratum corneum.