The aging process is known to be associated with profound changes in the heart. To determine whether resistance of coronary endothelial and vascular smooth muscle function to ischemia may be related to age, four groups of rats (n = 6 in each group) of different ages (1, 5, 15, and 26 months) were subjected to cardioplegic arrest for 4 hours at 4 degrees C. The postischemic basal release of nitric oxide by endothelium, as assessed by the percentage loss of coronary flow in response to 0.5 mmol/L L-monomethylarginine, an inhibitor of nitric oxide synthase, was as follows: (mean +/- standard error of the mean): 87.1% +/- 1.7%, 81.2% +/- 2.3%, 79.6% +/- 1.9%, and 74.9% +/- 2.4% in groups 1, 2, 3, and 4, respectively, Stimulated release of nitric oxide, as assessed by percentage increase of coronary flow to 10(-5) mmol/L 5-hydroxytryptamine, an endothelium-dependent vasodilator, was as follows (mean +/- standard error of the mean): 88.3% +/- 1.5%, 83.4% +/- 2.4%, 71.1% +/- 2.7%, and 63.1% +/- 3.3% in groups 1, 2, 3, and 4, respectively, Significant differences were found between each group (p < 0.05) for both basal and stimulated release of nitric oxide, Vascular smooth muscle function, as assessed by the percentage increase in coronary flow in response to glyceryl trinitrate, an endothelium-independent vasodilator, was (mean +/- standard error of the mean): 96.7% +/- 2.1%, 92.3% +/- 5.2%, 92.9% +/- 5.0%, and 98.1% +/- 2.4% in groups 1, 2, 3, and 4 respectively. No significant difference was found between groups (p = not significant), In a protocol mimicking conditions for transplantation, the postischemic recovery of the basal and stimulated release of nitric oxide, but not vascular smooth muscle function, diminished with age.