In newborns and adults of a number of species, exposure to acute hypoxemia produces a "regulated" decrease in core temperature, the mechanism of which is unknown. The present experiments were carried out on chronically instrumented newborn (5-10 days of age; n = 27) and older (25-30 days of age; n = 23) guinea pigs to test the hypothesis that adenosine mediates this regulated decrease in core temperature. During an experiment, core temperature was measured by biotelemetry from animals studied in a thermocline during a control period of normoxemia, an experimental period of normoxemia or acute hypoxemia (fraction of inspired oxygen 0.10), and during a recovery period of normoxemia after an intraperitoneal injection of 10 mg/kg aminophylline (i.e., a nonspecific adenosine antagonist) or vehicle. Core temperature decreased significantly during hypoxemia after vehicle in both newborn and older guinea pigs. After aminophylline, however, newborn guinea pigs failed to significantly decrease their core temperature, whereas older guinea pigs exhibited an attenuated yet significant core temperature decrease during hypoxemia. Our data support the hypothesis that adenosine plays an age-dependent role in mediating the regulated decrease in core temperature that occurs in newborn and older guinea pigs during acute hypoxemia.