Investigations have been carried out to explain the heterogeneity of response to catecholamines of human fat cells from various deposits. Adipocytes from two subcutaneous sites (abdominal and femoral) were studied concomitantly in women while omental fat cells were taken from another group of patients undergoing abdominal surgery. Alpha-2 and beta sites were identified in fat-cell membranes with [3H]yohimbine and [3H]dihydroalprenolol, respectively. Lipolytic responses were tested with isoproterenol (beta agonist), clonidine (alpha-2 agonist) and epinephrine. There are clear differences in the relative number of beta and alpha-2 sites according to the origin of the fat deposit; beta sites are less numerous than alpha-2 sites in subcutaneous fat cells of both regions (alpha-2:beta sites are in a ratio of 3 +/- 0.4:2 +/- 0.4). However, in membranes of omental fat cells, beta sites are at least as numerous as alpha-2 sites (ratio 0.9 +/- 0.2). Epinephrine always has a higher affinity for alpha-2 sites than for beta sites in the subcutaneous and omental deposits. In lipolysis studies, epinephrine, in the absence of adenosine in the incubation medium, initiated an anti-lipolytic effect in femoral fat cells and promoted inhibition of lipolysis at lower concentrations in abdominal subcutaneous fat cells, the effect being reversed at higher doses; epinephrine, however, was always lipolytic in omental adipocytes. There was no striking differences in the sensitivity to isoproterenol in the various deposits. Clonidine had a higher affinity for alpha-2 sites in femoral fat cells and was equipotent in the omental and abdominal ones. Thus, the differences in the lipolytic responses to epinephrine in adipocytes from different sites are linked to a variable alpha-2 inhibiting effect (and alpha-2 site number) rather than to a modified beta driven increase in lipolysis initiated by the physiological amine.