We studied the therapeutic potential of ex vivo vascular endothelial growth factor (VEGF) gene-transduced H9c2 cell transplantation for myocardial neovascularization. The left ventricular free wall of adult Sprague-Dawley rats was cryodamaged. Two weeks after, naked plasmid encoding VEGF (VEGF1: 1 1microg/100 microl, VEGF5: 5 microg/100 microl), or VEGF transfected H9c2 myoblasts (0.5 x 10(6) cells/200 microl) were injected into the center of scar tissue. Four weeks after cryoinjury, scar diameters in the each group were measured. Neovascularization in the scar tissue was then quantified histologically. Average scar tissue diameter 4 weeks after cryoinjury was as follows: TE (controls): 6.77 +/- 0.31 mm, H9c2: 5.08 +/- 0.43 mm; VEGF1: 5.90 +/- 0.20 mm; VEGF5: 4.50 +/- 0.24 mm. Scar tissue diameter was smaller in the 3 groups than in the control group (p < 0.05). Capillary density by histological examination increased in naked plasmid injection groups (VEGF1: 1,209.9 +/- 305.3/mm2; VEGF5: 1,072.0 +/- 230.8/mm2) versus controls (708.2 +/- 144.9/mm2, p < 0.05, p < 0.05), and H9c2 cell transplantation group (1,379.4 +/- 391.6/mm2) versus controls (p < 0.05). VEGF-transfected H9c2 myoblasts can be implanted and survive in infarcted myocardium. The ability to develop angiogenesis in the H9c2 cell transplantation group was markedly similar to direct myocardial injection in naked plasmid encoding VEGF groups.