The purpose of this study was to evaluate the effects of exogenous recombinant basic fibroblast growth factor (bFGF) on angiogenesis in severely ischemic tissue beds. We used a two-stage procedure to produce severe ischemia of the hindlimb of 34 New Zealand rabbits. The ischemic hindlimb received intramuscular injection of saline (group A), 1 μg bFGF (group B), or 3 μg bFGF (group C), daily for 2 weeks. Tissue perfusion, skeletal muscle infarction, angiogenesis, and collateral growth were assessed by angiography, transcutaneous oximetry (TcPo₂), quantitative spectrophotometric assay of triphenyltetrazolium chloride reduction in muscle, capillary density (capillaries per square millimeter), and capillary per muscle fiber ratio. There were no significant differences in baseline TcPo₂ among the three groups for both thigh and calf measurements. Angiography revealed extensive perfusion of the left hindlimb in all the assessed bFGF treated animals. Both thigh and calf TcPo₂ values showed a significant increase in all groups over the 14 days ischemia was induced (p < 0.0001), but the two treatment groups exhibited a much more rapid rise in TcPo₂ than the control group (p < 0.0001). The capillaries per square millimeter and capillaries per muscle fiber ratios were significantly increased in all posttreatment measurements for all animals that received bFGF. The treatment groups with bFGF had a significant (p = 0.025) increase in thigh muscle viability compared with controls based on triphenyltetrazolium chloride reduction. Whereas there was evidence of muscle infarction in both the thighs of groups A and B, there was none in group C. At the level of the calf, there was improvement in muscle viability in group B, but infarction was seen in both groups A and C (p = NS). The results in group C suggest that a high dose of bFGF in the thigh muscle may be protective, but in the more ischemic calf muscle may cause infarction. Generally there was a trend toward a dose-response effect for all posttreatment measurements except triphenyltetrazolium chloride reduction in the calf. We conclude that exogenous bFGF can enhance angiogenesis and growth of collaterals in a severely ischemic rabbit lower limb. (J Vasc Surg 1992;16:181–91.)