In contrast to cardiac purine metabolism, little is known about pyrimidine catabolism in heart. We therefore investigated uridine and uracil formation in ischemic rat and human hearts. Human donor hearts accumulated uridine 3 × (P < 0.05) before implantation. Hearts released this pyrimidine during implantation or correction of cardiac defects. During the former systemic blood uridine rose 38% (P < 0.05). In explanted human hearts, uridine was the only pyrimidine released during reperfusion; isolated, perfused rat hearts produced initially 3 × more uracil than uridine. Uridine phosphorylase activity in human heart homogenate was 3.4 mU/g wet weight, i.e. 60 × lower than that in rat myocardium (198 mU/g, P < 0.02); its purine counterpart, nucleoside phosphorylase, differed much less in activity (0.32 and 1.12 U/g, respectively; P < 0.001). Thus human heart is virtually devoid of uridine phosphorylase, contrasting rat heart. Consequently uridine accumulates in ischemic human heart while uracil production predominates in rat heart.