SUMMARYTachyphylaxis (acute tolerance) to two important actions of topical glucocorticosteroids is demonstrated. In humans, topically active glucocorticoids applied to the skin cause vasoconstriction initially but this response fades with successive applications. In hairless mouse epidermis, inhibition of DNA synthesis and mitosis is caused by one application of a glucocorticoid but with repeated administration of the drug this effect is lost. The degree of inhibition of cell division appears to be similar 30 and 54 h after one application of steroid to that following three or five applications during such a time period. These findings suggest that an optimum therapeutic approach to the use of these agents exists.