Effects of L-arginine, 300 mg/kg, i.p., on the regional cerebral blood flow (rCBF), brain metabolism, and infarct volume were examined in spontaneously hypertensive rats subjected to occlusion of both left middle cerebral artery and left common carotid artery. Rats treated with L-arginine had higher rCBF, determined by hydrogen clearance method, in the ischemic core (7 +/- 1 ml/100 g/min, mean +/- S.E.M.) and penumbral regions (16 +/- 2) than did rats treated with saline (5 +/- 0 and 7 +/- 1, respectively). Simultaneously, L-arginine attenuated metabolic derangement in the ischemic tissue at 60 min, i.e. well maintained adenosine triphosphate (ATP) in ischemic region (1.29 +/- 0.07 mmol/kg in L-arginine group vs. 1.05 +/- 0.06 in saline group), and also close to normal levels in ATP (2.61 +/- 0.02 mmol/kg vs. 2.45 +/- 0.05), glucose (2.29 +/- 0.12 mmol/kg vs. 1.80 +/- 0.17) and lactate (1.63 +/- 0.10 mmol/kg vs. 2.24 +/- 0.21) in periischemic region. In another experiment, the effects of L-arginine on rCBF in the subcortical regions and on infarct volume were evaluated. L-arginine, compared with saline, increased rCBF by 8 ml/100 g/min in the ischemic side and reduced infarct volume by 29% at 24 h of ischemia. These findings support that L-arginine may be potentially useful for the treatment of acute cerebral ischemia.