The purpose of this study was to evaluate the vasoformative response of isolated vascular explants to a variety of growth factors that have been shown to stimulate angiogenesis. Rings of rat aorta were cultured in collagen gels under serum-free conditions in the presence or absence of vascular endothelial growth factor (VEGF), natural platelet-derived growth factor (PDGF), PDGF-AA, PDGF-BB, insulin-like growth factor-1 (IGF-1), transforming growth factor-alpha (TGF-alpha), transforming growth factor-beta 1 (TGF-beta 1), epidermal growth factor (EGF), interleukin-1 alpha (IL-1 alpha), or hepatocyte growth factor (HGF). The angiogenic response of the rat aorta was stimulated by VEGF, PDGF, PDGF-AA, PDGF-BB, and IGF-1. Maximum stimulatory effects were obtained with VEGF and PDGF-BB. By contrast, TGF-beta 1 and IL-1 alpha had inhibitory activity. No significant effects were observed with TGF-alpha, EGF, or HGF. The vascular outgrowth of VEGF-stimulated cultures was primarily composed of microvessels, whereas that of PDGF- and IGF-1-stimulated cultures contained an increased number of fibroblast-like cells. The inability of TGF-alpha, TGF-beta 1, IL-1 alpha, EGF, and HGF to stimulate rat aortic angiogenesis in serum-free culture suggests that either these factors require the mediatory activity of accessory cells that are not present in the rat aorta model or that blood vessels are heterogeneous in their capacity to respond to different angiogenic factors.