The free fatty acids have been implicated by indirect evidence in the pathogenesis of acne vulgaris. A determination of the relative irritancy of different chain lengths of these acids therefore assumed major importance. The even numbered free fatty acids from C2 to C16 were repeatedly applied under occlusive patch tests to human skin. Free fatty acids penetrated the epidermal barrier and produced inflammation. Greater irritancy or penetration or both by the C8 to C14 range of fatty acids, particularly by the C12 fatty acid, was found. Although this study did not reproduce the pathophysiologic conditions that occur in acne vulgaris, the results suggest that the search for differences in the fatty acid spectrum of patients with acne should be focused on the C8 to C14 range of fatty acids.