When 1,4-sorbitan and 1,4,3,6-dianhydrosorbitol were substituted for the sugar alcohol in Span 60 (sorbitan monostearate) and Tween 60 (polyoxyethylene sorbitan monostearate), and the resulting products ≈0.18 m aqueous dispersions and solutions were painted 6 times a week on the mouse skin, the alterations in the skin of the back of the mouse corresponded to those caused by the original Span 60 and Tween 60, respectively. The Span 60-type products 1,4-sorbitan monostearate, 1,4-sorbitan distearate, 1,4-sorbitan tristearate, 1,4,3,6-dianhydrosorbitol monostearate, and 1,4,3,6-dianhydrosorbitol distearate were almost inactive. The Tween 60-type products polyoxyethylene-1,4-sorbitan monostearate, polyoxyethylene-1,4-sorbitan distearate, polyoxyethylene-1,4-sorbitan tristerate, and polyoxyethylene-1,4,3,6-dianhydrosorbitol monostearate produced an immediately developing, high-degree, and regular epidermal hyperplasia. The evolution, general development, and nature of this hyperplasia were similar in all respects to those produced by Tween 60. This is one fact in favor of the significance of the physicochemical nature of a fatty acid ester-type agent which causes hyperplasia.