Background. Therapeutic angiogenesis in ischemic myocardium has been shown to be a feasible and effective strategy to improve regional blood now and myocardial function. However, the optimal mode of growth factor administration still needs to be established. Methods. Using a pig model of chronic myocardial ischemia, we evaluated the efficacy of intravenous and intracoronary infusion of FGF-2 at 2 and 6 mug/kg compared with a vehicle control. Improvement in myocardial perfusion and function was assessed by angiography, colored microspheres, and function and perfusion magnetic resonance imaging. Results. Intracoronary 6-mug/kg FGF-2 increased angiographic collaterals (p = 0.046) and increased regional blood now to the ischemic area from 0.36 +/- 0.07 to 0.59 +/- 0.08 mL/min/g at stress (vs control, p = 0.032). Also, after 6 mug/kg intracoronary FGF-2, ejection fraction, regional wall motion, and thickening improved significantly by 9.9% +/- 1.9%, 126% +/- 39%, and 13.8% +/- 3.6%, respectively. Intravenous FGF-2 and intracoronary 2 mug/kg FGF-2 were ineffective. Conclusions. A single 6-mug/kg intracoronary treatment with FGF-2 resulted in significant improvement in collateralization and regional and global function of chronically ischemic myocardium. Single intravenous infusion of FGF-2 was not effective in this model. (Ann Thorac Surg 2000;70:2113-8).