The effect of the chronic oral application of NG-nitro-L-arginine methyl ester (L-NAME), a potent inhibitor of nitric oxide (NO) production, was studied on hypothalamic blood flow (HBF) and hypothalamic nitric oxide synthase (NOS) activity in rats. L-NAME was dissolved in the drinking water, in a concentration of 0.1 mg/ml, and was administered for 1 week. In the chronic L-NAME pretreated animals significantly reduced hypothalamic NOS activity and marked hypothalamic vasoconstriction were observed, the latter of which was counteracted by sustained systemic arterial hypertension, while HBF remained unchanged. The present model of chronic NOS blockade may be useful to assess the physiological functions of NO in the regulation of cerebral blood flow in the normally perfused brain.