We tested the hypothesis that inhibition of nitric oxide synthase (NOS) activity in brain before ischemia decreases postischemic hyperemia. Pentobarbital-anesthetized piglets underwent 15 min of complete global cerebral ischemia induced by elevation of intracranial pressure followed by 20 min of reperfusion. Before ischemia the animals were randomly assigned to receive either intravenous N omega-nitro-L-arginine methyl ester (L-NAME 10 mg/kg, n = 6, or 50 mg/kg, n = 6) or an equal volume of saline (10 ml, n = 8). Serial cerebral blood flow (radiolabeled microspheres) was measured at baseline and during ischemia and reperfusion. Forebrain postischemic hyperemia was documented after administration of saline (42 +/- 4 to 88 +/- 10 ml.min-1.100 g-1) and 10 mg/kg L-NAME (36 +/- 4 to 59 +/- 9 ml.min-1.100 g-1) but not after 50 mg/kg L-NAME (29 +/- 3 to 34 +/- 7 ml.min-1.100 g-1). However, the percent reduction in cerebral vascular resistance (CVR) fell during reperfusion to a similar extent in all three groups because of differences between groups in cerebral perfusion pressure changes during the protocol. CVR fell to the lowest level at 8 min of reperfusion in the saline-treated animals (2.0 +/- 0.16 to 0.68 +/- 0.05 mmHg.ml-1.min.100 g) compared with the L-NAME-treated animals (50 mg/kg: 4.0 +/- 0.3 to 1.8 +/- 0.2 mmHg.ml-1.min.100 g).(ABSTRACT TRUNCATED AT 250 WORDS)