The effect of exogenous glutamic acid and arginine on the contractility of isolated perfused rat heart and on the metabolism of some nitrogenous compounds was studied. Sixty-minute anoxic perfusion (95% N2 + 5% CO2) led to a fall in developed isovolumic pressure and an elevation in diastolic pressure, to an increase in the production of alanine, glutamine, and ammonia, and to a decrease in the tissue content of aspartate and glutamate. The total pool of free amino acids and taurine under these conditions remained unchanged. Subsequent 40-min reoxygenation partially restored the contractile function. Addition of 3.5 mM glutamic acid or 5 mM arginine into the perfusate before anoxia resulted in a higher level of developed pressure and a lower level of diastolic pressure during anoxia and almost complete recovery of cardiac function after subsequent reoxygenation. Both amino acids had no effect on ammonia formation by the anoxic heart but enhanced its binding in myocardial tissue via formation of glutamine and urea. It is suggested that the exogenous amino acid effect on anoxic heart is mediated by activation of substrate phosphorylation rather than the ability to bind tissue ammonia.