The metabolism of pyrimidine nucleotides in the myocardium is poorly understood. The turnover of these nucleotides is high, whereas their concentration is rather low The de novo pathway of synthesis does not seem very efficient, although the utilization of nucleosides could represent the major pathway for pyrimidine nucleotide synthesis. In rat blood, cytidine could be the major precursor for pyrimidine nucleotide synthesis. The precursor, whatever its exact nature (uridine or cytidine), could be species dependent, and the liver could play a major role in providing blood nucleosides. Owing to the essential role of pyrimidine nucleotides in the synthesis of macromolecules, acute or chronic alteration of the metabolism of these nucleotides could have crucial consequences on heart viability and function. Providing pyrimidine precursors to the heart, isolated or in situ, induces functional and metabolic effects on the heart. The experimental results suggest that such interventions could be beneficial in clinical situations such as cardioplegia, heart preservation, or recovery from ischemia.