The influence of fasting on the dual adrenergic control of adipose tissue lipolysis was investigated in hamsters because in this species the adipocytes exhibit both beta-stimulatory and alpha 2-inhibitory adrenergic responses. In adipocytes from fed animals, the number of alpha 2-receptors (identified with [3H]clonidine and [3H]RX 821002) was greater than that of beta-receptors. As in humans, the alpha 2-adrenoceptor number was greater in adipocyte membranes from subcutaneous (inguinal and popliteal) than from internal (perirenal and epididymal) adipose tissues. Despite this difference in alpha 2-adrenoceptor number, the antilipolytic responses to the alpha 2-agonists clonidine and UK 14304 were similar in the two tissues. Food deprivation for a period of 1-6 days induced a net depletion of both adipose tissues. In 6-day starved animals the number of adipocyte alpha 2-adrenoceptors and the maximal antilipolytic effect of UK 14304 were less than 50% of those in fed controls. In contrast, the antilipolytic responses to phenylisopropyladenosine or prostaglandin E1 remained unchanged. Starvation induced a decrease in alpha 2-adrenoceptor number and an increase in beta-adrenergic sensitivity that were greater in adipocytes from subcutaneous than from internal fad pads. The data suggest that the adipocyte beta- and alpha 2-adrenoceptors are independently regulated during starvation. In the adipocyte, the alpha 2-antilipolytic responses and the alpha 2-adrenoceptor levels are dependent on the extent of the adipose mass; they are particularly reduced in emaciated hamsters.