The effect of adenosine and inosine on food consumption was tested by a 4 hr satiety assay in rats fasted overnight who then received injections subcutaneously, and also in ad libitum fed rats infused intravenously for 24 hr periods. It was found that adenosine, and to a lesser degree inosine, produced a significant suppression of food intake (86 and 69% reduction from control, respectively) during the 1st hr after subbcutaneous injection. This effect persisted for 4 hr, at the end of which both substances produced an average 37% reduction in food intake from control values. This effect of adenosine was also found in ad libitum-fed animals infused intravenously with adenosine for 24 hr (35% reduction from control). These studies report a previously undescribed effect of adenosine and add another substance to the list of agents shown to influence food intake regulation. Since adenosine is known to play a local regulatory role on adipose tissue metabolism and is generated and released from adipose tissue, the present findings may indicate an additional role for adenosine in providing a feedback regulatory signal between the adipose organ and the hypothalamic centers of food intake regulation.