1. In ten spontaneously breathing, Saffan-anaesthetized rats (group I), respiratory and cardiovascular responses evoked by 10 min periods of hypoxia (arterial partial pressure of O2, Pa,O2, 33 mmHg) were recorded before and after the administration of the adenosine receptor antagonist 8-phenyltheophylline (8-PT, 10 mg kg-1 i.v.). Similar experiments were performed on nine constantly ventilated rats (group II; Pa,O2, 29 mmHg) with arterial partial pressure of CO2 (Pa,CO2) held constant. 2. In group I, hypoxia induced an initial increase and a secondary fall in ventilation (VE) with an accompanying secondary fall in heart rate (HR), arterial pressure (ABP) fell and cerebral vascular conductance (CVC) increased progressively. Cerebral blood flow (CBF) tended to fall with time during hypoxia. 8-PT abolished the secondary falls in VE and HR and reduced the fall in ABP and increase in CVC, while CBF was better maintained. 3. In group II, hypoxia induced a similar cardiovascular response to that in group I, but at the 1st minute of hypoxia, the HR was lower and the increase in CVC was greater. 8-PT did not affect the hypoxia-induced changes in HR, ABP, CVC or CBF. 4. These results indicate specific ways in which the ventilatory and cardiovascular responses induced by hypoxia in the spontaneously breathing rat are interdependent. They also indicate that the influences of 8-PT on the cardiovascular changes induced by hypoxia during spontaneous ventilation are mainly a consequence of its ability to block the centrally mediated contribution of adenosine to the secondary fall in ventilation.