Systemic absorption of topically applied glucocorticoids in quantities sufficient to replace endogenous production is not uncommon. However, iatrogenic Cushing's syndrome resulting from the use of topical corticosteroids is very rare. Thus the possibility that systemic absorption may cause hyperglucocorticism has been deemphasized and examined only sporadically. We have studied changes in carbohydrate metabolism induced by topical glucocorticoids in a psoriatic patient who had developed Cushing's syndrome from topical desoximetasone (Topicort). The results indicated that (1) fasting hyperglycemia and increased insulin-glucose ratios could be induced within 24 hours of administration of topical glucocorticoids, (2) insulin resistance accompanied abnormal carbohydrate tolerance, and (3) fluctuations in circulating leukocytes paralleled the changes in carbohydrate metabolism. The findings suggest that metabolic indexes of glucocorticoid action may provide useful parameters for assessing systemic absorption of topical glucocorticoids. Our report demonstrates the feasibility of using the insulin-glucose relationship as one such index to assess the risk of treatment of extensive chronic skin disease with potent topical glucocorticoids.