Background Collateral growth is induced by chemical signals from the ischemic myocardium. We hypothesized that angiogenic growth factors are produced by cardiac tissue; they are diffusible, more concentrated in pericardial fluids, and are increased by myocardial ischemia. Methods and Results With the use of an enzyme-linked immunosorbent assay, we measured the concentrations of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) in pericardial fluids of 12 patients with unstable angina (group 1) and of 8 patients with nonischemic heart diseases (group 2). The levels of protein in pericardial fluids were quite comparable between the two groups (34+/-2 versus 32+/-4 mg/mL). The concentration of bFGF in pericardial fluids in group 1 was 2036+/-357 pg/mL, significantly (P <.001) higher than the 289+/-72 pg/mL in group 2. The amount of bFGF per milligram of protein was also significantly (P <.05) higher in group 1 than in group 2 (67+/-15 versus 12+/-4 pg/mg). The concentration of VEGF in pericardial fluids tended to be higher in group 1, but the difference was statistically insignificant (39+/-7 versus 22+/-6 pg/mL). The amount of VEGF per milligram of protein was 1.2+/-0.3 pg/mg in group 1, similar to the 0.8+/-0.4 pg/mg in group 2. Conclusions This finding provides new evidence that bFGF plays an important role in mediating collateral growth in humans.