This study was designed to clarify whether nitric oxide (NO) participates in the regulation of local cerebral blood flow (CBF) during hypoxia (inhalation of 15% O(2) in N(2)). The CBF response to hind-paw stimulation (evoked CBF) of Sprague-Dawley (SD) rats was measured by laser-Doppler flowmetry. Physiological variables, such as heart rate, mean blood pressure, and PaCO(2) during hypoxia, were identical to those under normoxic conditions. Hypoxia increased the baseline CBF (17.5 ± 14.3%) and the normalized peak amplitude of evoked CBF (31.1 ± 18.5%) relative to those during normoxia. When an NOS inhibitor was infused intravenously, these differences were abolished in both the baseline CBF or evoked CBF between normoxic and hypoxic conditions, whereas the heart rate decreased and the mean blood pressure increased during hypoxia in comparison with these during normoxia. The field potential was constant under all experimental conditions. These results suggest that NO plays a major role in the regulation of baseline and evoked CBF during hypoxia.