The in vitro relationship between fat-cell size, glycerol release, and peak concentration of cyclic AMP was investigated in human adipose tissue obtained from 25 obese nondiabetic patients before and after a 7-day fast and from 23 patients with untreated diabetes mellitus. In the obese nondiabetic patients there was a linear correlation between fat-cell size and cyclic AMP concentration, and fat-cell size and the rate of lipolysis. This was found both in nonfasting and fasting nondiabetic patients. However, in diabetes mellitus, there was only a relationship between cell size and cyclic AMP concentration. The alpha-adrenergic and beta-adrenergic activity in human adipose tissue was assessed by comparing the effect of isoprenaline and noradrenaline on the cyclic AMP concentration. The activity of both receptors was found to be increased in fasting obese patients and in diabetics. In both conditions the alpha-adrenergic response to catecholamines predominated in small fat cells, whereas in large ones the beta response predominated. The results suggest that during fasting and in diabetes mellitus there is a correlation between fat-cell size and the responsiveness of the adrenergic receptors. Thus, catecholamines may be involved in regulating the fat-cell volume. The view is expressed that the abnormal catecholamine-induced lipolysis is solely due to changes at the level of the adrenergic receptors during fasting, whereas in diabetes mellitus the sequentional activation of lipolysis is disturbed at deeper sites as well.