Angiogenesis is one of the most important features of AIDS-associated Kaposi's sarcoma (AIDS-KS). Our studies suggested that spindle-shaped AIDS-KS cells from various AIDS-KS lesions play important roles in the development of KS lesions. Basic fibroblast growth factor (bFGF) has been reported to be a predominant angiogenic factor expressed in AIDS-KS cells. However, our data from ELISA revealed the presence of the vascular endothelial growth factor (VEGF) molecule in large quantities in AIDS-KS cell-derived conditioned medium (AIDS-KS-CM) (12.1-21.4 ng/ml). In contrast, small amounts of bFGF were detected in AIDS-KS-CM (76-245 pg/ml). The combination of anti-VEGF and anti-bFGF IgGs completely inhibited endothelial cell growth-promoting activities in AIDS-KS-CM, while activities partially remained in the presence of anti-bFGF IgG or anti-VEGF IgG alone. VEGF and bFGF in AIDS-KS-CM were distinguished by heparin-affinity chromatography. Furthermore, the combination of VEGF and bFGF synergistically augmented the growth of endothelial cells. Both VEGF and bFGF revealed an angiogenic property that was inhibited by specific Abs, when applied to the rabbit cornea and chicken chorioallantoic membrane. On Western blots, anti-VEGF IgG gave two major bands of 22 and 24 kDa, similar to those of recombinant VEGF165. As detected on Northern blots, AIDS-KS cells expressed major 3.9-kb VEGF-specific mRNA. Thus, VEGF, in concert with bFGF, may play a crucial role in the angiogenesis of AIDS-KS lesions.