Administration of adenosine and agonists of the adenosine receptors to rats results in hypoactivity, hypothermia, muscle relaxation and antinociception. In the present study, we found that the adenosine ligand, N6-R-phenylisopropyladenosine (R-PIA), increased food intake in rats at a time in the day when rats normally eat very little food or none at all. Feeding was not reliably stimulated upon the first exposure to R-PIA, but was clearly increased following repeated administration of this agonist. Other adenosine agonists, namely 2-chloradenosine and 5'N-ethylcarboxamide adenosine, failed to alter feeding after a single injection or after repeated exposure. The adenosine antagonist, caffeine, did not block R-PIA's effect on food intake, whereas the opioid antagonist, naloxone, blocked R-PIA-induced eating. These data suggest that R-PIA stimulates feeding independent of the A1 or A2 adenosine receptors.