Using isolated white fat cells of the hamster, we studied the possible inhibitory effects on lipolysis of the preferentially selective alpha-1-adrenoceptor blocking and anti-hypertensive agent prazosin. Parallel studies were undertaken with the preferentially alpha-2-adrenoceptor blocking agent yohimbine. Neither of the compounds had any significant effects on basal (non-stimulated) lipolysis. When lipolysis was stimulated by noradrenaline or isoprenaline, however, prazosin showed significant anti-lipolytic effects from a concentration of 10(-6) M. Lipolysis stimulated by methylisobutylxanthine was antagonized by prazosin only at a concentration of 10(-4) M, and dibutyrylcyclic adenosine 3'5' monophosphate-stimulated lipolysis was not inhibited at all. It is suggested that prazosin inhibits lipolysis by preventing adenyl cyclase activation by an indirect mechanism not identifiable with an alpha-2-adrenergic function but associated possibly with the formation of a local inhibitory mediator. These observations are compatible with a reduction of the outflow of free fatty acids from adipose stores in patients undergoing prazosin therapy and thus a breaking of the "vicious circle" leading to elevated plasma lipoproteins and may explain, in part at least, the reduction in plasma lipid levels observed during prazosin treatment in man.