This study was designed to evaluate the effect of smooth muscle cell transplantation into myocardial ventricular scar formed by cryo-necrosis. The left ventricular free wall (LVFW) of adult rats was cryo-necrosed. At 4 weeks after cryo-injury cultured fetal rat stomach smooth muscle cells (transplanted group,n=10) or culture medium (control,n=10) were transplanted. Sham animals (n=8) were similarly operated but without cryo-necrosis and transplantation. The animals were administered a daily maintenance dose of cyclosporin A (5 mg/kg). At 8 weeks after cryo-injury, heart function was evaluated using a Langendorff preparation. Myocardial scar and transplanted cells were assessed histologically. Transplanted smooth muscle cells survived and formed smooth muscle cell tissue, as assessed by immunostaining against smooth muscle cell actin, within the myocardial scar. In the control hearts no muscle tissue was found in the scar. Angiogenesis occurred (P<0.001) in the transplanted scar compared to the control scar. The transplanted cells increased the scar thickness (P<0.01) by hyperplasia and prevented (P<0.001) the dilatation of the ventricular chamber size compared to the control hearts. For physiological left ventricular volumes of 0.04 to 0.28 ml, the systolic and developed pressures in the transplanted group were greater (P<0.001) than the control group, but less (P<0.001) than those of the sham group. Transplanted smooth muscle cells formed smooth muscle tissue in myocardial scar tissue and improved contractile function compared to control hearts.