The role of nitric oxide in the cerebral circulation under basal conditions and when exposed to hypoxic, hypercapnic and hypotensive stimuli, was studied in mechanically ventilated rats using a venous outflow technique, by examining the effects of inhibition of nitric oxide synthase with N-nitro-L-arginine methyl ester (L-NAME). L-NAME (10 or 30 mg/kg injected intravenously) raised mean arterial blood pressure by 14% and 24%, and increased cerebrovascular resistance (CVR) by 20% and 24%, respectively. Cerebral blood flow (CBF) was unaltered, as were blood gases and pH. The increases in MABP and CVR were attenuated by L-arginine (300 mg/kg). Following the administration of L-NAME, the increases in CBF elicited by ventilation with 8% oxygen for 25 s were unaltered, in comparison to control responses. L-NAME attenuated the increases in CBF and reduced the time for recovery to basal flow rates evoked by ventilation with 10% carbon dioxide. These effects were reversed by L-, but not by D-, arginine. Autoregulation by CBF during hypotensive episodes, as measured by comparisons of CVR values, was unaffected by L-NAME. The results suggest that endogenous nitric oxide is involved in the responses of the cerebral vasculature to elevated levels of CO2 in the arterial blood. Nitric oxide does not appear to play a major role in autoregulation to increases or decreases in MABP, or in hypoxia-evoked vasodilation.