Subcutaneous adipose tissue was obtained from 9 patients with untreated diabetes mellitus and from 13 obese nondiabetics. After incubation with isoprenaline or noradrenaline, glycerol release and tissue cyclic AMP (cAMP) were determined. Basal glycerol release was twice as rapid from the diabetic adipose tissue. With isoprenaline, the cAMP concentration and the glycerol production was significantly higher in the diabetic adipose tissue. Noradrenaline did not increase glycerol production or cAMP concentration in the diabetic adipose tissue. Subcutaneous adipose tissue was also removed from the diabetics after antidiabetic treatment. Basal lipolysis was significantly reduced and noradrenaline significantly increased both glycerol release and cAMP production. With isoprenaline, cAMP production and glycerol release were significantly less after antidiabetic treatment than in the untreated state. The data provide evidence for increased a- as well as fl-adrenergic receptor sensitivity in human subcutaneous adipose tissue of untreated diabetic patients