The Hemolytic Uremic Syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia and acute renal failure. The ability of an infectious agent to injury microvascular endothelial cells is a primary requisite for the development of HUS. To investigate potential growth factors released during endothelial injury that could be implicated in the pathogenesis of HIV-HUS, we tested the ability of urine samples obtained from two patients with HIV-HUS to stimulate the growth of renal mesangial, epithelial and endothelial cells. Control samples were obtained from five HIV infected children without renal disease. Concentrated (5X) urine samples derived from children with HIV-HUS, induced normal vascular endothelial cells to acquire “spindle cell morphology ”, to proliferate, and to form tube-like structures when these cells were grown on a reconstituted basement membrane. Since bFGF has been implicated in the pathogenesis of HIV associated Kaposi's sarcoma (KS), and is known to induce these endothelial cell behaviors, we performed heparin Shepharose column chromatography. Western blot analysis performed in HIV-HUS urinary fractions eluted with 1.5 M NaCl, revealed a 18 kDA band, consistent with the presence of bFGF in the urine of both patients. By radioimmunoassay, we found increased bFGF in the plasma and urine of children with HIV-HUS. Immunohistochemistry studies using specific bFGF antibodies revealed increased expression of bFGF in renal cortex, medulla and extracellular matrix surrounding renal tubules. Renal tubular epithelial cells (RPTEc) isolated from HIV-HUS patients released bFGF into the conditioned media, and proliferate in response to bFGF. Thus, the accumulation of bFGF in the kidney of children with HIV associated HUS may be one of the mechanisms for the induction and progression of this syndrome. The ability of HIV-1 to induce endothelial cell injury and bFGF release may play a relevant role in the pathogenesis of HIV associated HUS.