The effects of the activation of adenosine receptors on core body temperature of mice have been studied in the present investigation. Intraperitoneal (i.p.) injection of non-selective adenosine agonists 5'-N ethyl- carboxamide adenosine (NECA; 0.001, 0.01 and 0.05 mg/kg), R-(N(6)-phenylisopropyl)-adenosine (R-PIA; 0.01, 0.1 and 0.25 mg/kg) and selective A(1) adenosine agonist N(6)-cyclohexyladenosine (CHA; 0.1, 0.25 and 0.4 mg/kg) reduced core body temperature. However, R-PIA and CHA were less potent than NECA in reducing the core body temperature. Theophylline (12.5, 25 and 50 mg/kg) blocked the hypothermia of the adenosine agonists. Pre-treatment of animals with selective A(1) adenosine antagonist 8-phenyltheophylline (8-PT; 0.5, 1 and 2 mg/kg) decreased the hypothermic response of CHA but not of NECA and R-PIA. 8-PT potentiated the hypothermia induced by R-PIA. These results suggest that activation of both A(1) and A(2) adenosine receptors decreases core body temperature in mice.