Growth factor-induced angiogenesis is being investigated in ischemic heart disease. Intracoronary and intravenous delivery are the most practical, but are limited by low myocardial uptake and significant systemic recirculation. The pericardial space may act as a drug delivery reservoir with increased myocardial uptake and reduced systemic toxicities. This study was designed to investigate the myocardial and tissue deposition and retention of basic fibroblast growth factor (FGF-2) after intrapericardial administration in normal and chronically ischemic animals. Twelve Yorkshire pigs were used for the study [six normal and six animals with chronic myocardial ischemia (ameroid constrictor on LCx)] with bolus intrapericardial administration of (125)I-FGF-2 (25 micro Ci) with 30 micro g of cold FGF-2 and 3 mg of heparin. Tissue and myocardial distribution was determined at 1 and 24 hr by measuring (125)I-bFGF-specific activity. In addition, regional myocardial deposition was determined using (125)I-bFGF activity and organ level autoradiography. The heart (pericardium and myocardium) accounted for the majority of (125)I-bFGF activity in ischemic animals (30.9% at 1 hr and 23.9% at 24 hr). Left anterior descending artery territory activity/gm of tissue for nonischemic and ischemic animals was 0.01% and 0.01% at 1 hr and 0.0009% and 0.12% at 24 hr, respectively. LCx territory activity for nonischemic and ischemic animals was 0.006% and 0.008% at 1 hr and 0.03% and 0.05% at 24 hr, respectively. Endocardial activity was low at all time points. Liver uptake was 0.47% (nonischemic) and 0.34% (ischemic) at 1 hr and 0.23% (nonischemic) and 0.54% (ischemic) at 24 hr. Intrapericardial delivery of FGF-2 provides markedly higher myocardial deposition and retention and lower systemic recirculation than intracoronary or intravenous delivery at the expense of poor subendocardial penetration. This limitation, however, did not affect its efficacy.