The effects of two different kinds of stress (social and physical) on central adenosine receptors were investigated in mouse whole brain membranes using 1,3-diethyl-8-[3H]phenylxanthine ([3H]DPX) as a ligand. Chronic but not acute social stress induced an increase in the number of adenosine receptors similar to that induced by chronic, nontoxic doses of caffeine. Acute but not chronic social stress also induced an increase in the number of benzodiazepine receptors labeled by [3H]beta-carboline-3-carboxylate ethyl ester. The group submitted chronically to both stress and caffeine showed an increase in [3H]DPX binding relative to that found with either of these factors alone. The adenosine uptake site, labeled by [3H]nitrobenzylthioinosine, was not modified by either stress or caffeine administration.