The effects of gene transfer of the secreted form of fibroblast growth factor-2 (FGF-2) were tested using an adenovirus vector in the microembolized rabbit heart. Japanese white rabbits underwent an intracoronary injection of 25-mum microspheres followed by recombinant adenovirus vectors encoding a secreted form of FGF-2 (FGF group), LacZ (LacZ group), or saline (saline group). Left ventricular (LV) systolic function was serially assessed by echocardiography, Vascular density was measured at 14 days with Azan and CD31 staining. The development of collateral vessels was assessed by measuring myocardial brood flow before and after the occlusion of the left anterior descending coronary artery. Percent fractional shortening (%FS) decreased after the microembolization, and improved gradually for 14 days in the FGF group only (41+/-1% (FGF) vs 32+/-1% (LacZ), 31+/-1% (saline), p<0.01). The vascular density and myocardial collateral blood flow were significantly higher in the FGF group in comparison with other groups. Transcoronary arterial gene transfer of the secreted form of FGF-2 was beneficial for the recovery of LV systolic function and development of collateral vessels in the microembolized rabbit heart.