Objectives: Transplantation of fetal cardiomyocytes improves function of infarcted myocardium but raises availability, immunologic, and ethical issues that justify the investigation of alternate cell types, among which skeletal myoblasts are attractive candidates. Methods: Myocardial infarction was created in rats by means of coronary artery ligation. One week later, the animals were reoperated on and intramyocardially injected with culture growth medium alone (controls, n = 15), fetal cardiomyocytes (5 x 106 cells, n = 11), or neonatal skeletal myoblasts (5 x 106 cells, n = 16). The injections consisted of a 150-μL volume and were made in the core of the infarct, and the animals were immunosuppressed. Left ventricular function was assessed by echocardiography immediately before transplantation and 1 month thereafter. Myoblast-transplanted hearts were then immunohistologically processed for the expression of skeletal muscle-specific embryonic myosin heavy chain and cardiac-specific connexin 43. Results: The left ventricular ejection fraction markedly increased in the fetal and myoblast groups from 39.3% ± 3.9% to 45% ± 3.4% (P = .086) and from 40.4% ± 3.6% to 47.3% ± 4.4% (P = .034), respectively, whereas it decreased in untreated animals from 40.6% ± 4% to 36.7% ± 2.7%. Transplanted myoblasts could be identified in all animals by the positive staining for skeletal muscle myosin. Conversely, clusters of connexin 43 were not observed on these skeletal muscle cells. Conclusions: These results support the hypothesis that skeletal myoblasts are as effective as fetal cardiomyocytes for improving postinfarction left ventricular function. The clinical relevance of these findings is based on the possibility for skeletal myoblasts to be harvested from the patient himself.