The systemic effects of topically applied 0.1% hydrocortisone 17-butyrate during treatment with and without occlusion were measured in terms of the functions of the pituitary-adrenal axis. Corticosteroid levels in the blood were determined by the modified method of Murphy, a competitive protein-binding radioassay. Circulating eosinophils were counted and the urinary 17-OHCS and 17-KS excretion were also determined. Percutaneous absorption following the topical application of 14C hydrocortisone 17-butyrate1 (HC 17-B, Locoid®) was measured by means of autoradiography. The application of the corticosteroid to the normal skin without occlusion did not induce systemic effects, whilst the application of the drug under occlusive dressing showed that systemic effects may possibly be induced. The number of circulating eosinophils, corticosteroid levels in the blood and urinary 17-OHCS excretion all decreased. However, these values returned to normal about 2 days after the withdrawal of the application, so we consider the systemic effects induced by the topical corticosteroid to be of a temporary nature. The percutaneous absorption of the corticosteroid was proved by an autoradiographic technique using 14C-labelled HC 17-B. At various intervals after the application, radioactive substances were observed as silver grains in the horny layer of the epidermis and skin appendages, and the density of the silver grains gradually increased with the course of time. It may be surmised that locally applied HC 17-B will be retained in the horny layer of the epidermis at a very early stage after the application and then absorbed in the blood via the epidermis and skin appendages. The reservoir of the corticosteroid in the skin was demonstrated 24 h after the withdrawal of the application