Biopsies of human adipose tissue were maintained for 1 wk in vitro with physiologic (1.5-30 X 10(-8) M) or pharmacologic (300 X 10(-8) M) concentrations of hydrocortisone or 1000 muU/ml insulin, or both. After this period, the explants were washed and incubated for 2 hr according to techniques generally used to study fat cell metabolism. Physiologic concentrations of hydrocortisone mainly exert an insulin antagonistic effect. Thus, the long-term effects of insulin in increasing lipolysis, as well as glucose metabolism to triglycerides, were reduced, as were the acute effects of insulin on these parameters. At these concentrations, the glucocorticoid itself did not influence the basal metabolic rates when due consideration was given to simultaneous changes in mean fat cell size. At higher concentrations, which may easily be reached during nonspecific glucocorticoid therapy, the glucose metabolism was reduced. Hydrocortisone decreased the number of insulin receptors. However, this cannot solely explain the insulin-antagonistic effect, since it was not overcome by a supramaximal concentration of insulin. Insulin and hydrocortisone together increased the lipoprotein lipase (lpl) activity several times. The resultant changes in LPL appear to depend upon the insulincorticosteroid ratio.