The protective effect of L-arginine on ischaemia/reperfusion-induced myocardial injury was investigated in the rat isolated Langendorff perfused heart. Six groups of hearts subjected to 30 min global ischaemia and 30 min reperfusion received either vehicle, D-arginine, L-arginine, the nitric oxide (NO)-donor S-Nitroso-N-Acetyl-D, L-Penicillamine (SNAP), the inhibitor of NO formation NG-nitro-L-arginine (L-NNA), or L-arginine plus L-NNA. The recoveries of left ventricular double product and coronary flow at the end of reperfusion were significantly higher in the L-arginine group (85 +/- 5 and 75 +/- 6%, respectively) than in the vehicle group (37 +/- 6 and 34 +/- 5%, respectively, P < 0.05). During both the ischaemic and reperfusion periods, left ventricular end diastolic pressure was lower in the L-arginine group than in the vehicle group. Creatine kinase outflow and the area of no-reflow were smaller in the L-arginine treated hearts (P < 0.01). There were no differences between vehicle and D-arginine treated groups. L-NNA did not affect recovery per se but abolished the protective actions of L-arginine. SNAP produced the same protective effects as L-arginine. Acetylcholine-induced endothelium-dependent vasodilation was reduced after ischaemia and reperfusion in the vehicle group but not in the L-arginine group. It is concluded that L-arginine reduces ischaemia/reperfusion-induced myocardial and endothelial injury. The results suggest that the beneficial effects of L-arginine are related to preserved synthesis and release of NO.