The ability of Shiga-like toxins to injure renal microvascular endothelial cells is a primary requisite for the development of HUS. We hypothesized that growth factors released during endothelial injury may play a relevant role in the pathogenesis of classic HUS. In a preliminary screening of vascular growth factors in the urine of ten children affected with classic HUS, we found significant levels of FGF-like activity. Further purification of the most active fractions by heparin Shepharose column chromatography revealed an 18 kDA band consistent with the presence of bFGF. By radioimmunoassay, we found very high plasma levels of bFGF in HUS affected children (156 ± 24 pg/ml) when compared to control children (12 ± 4 pg/ml P< 0.005). Immunohistochemistry studies using specific bFGF antibodies revealed increased expression of bFGF in renal cortex, medulla and extracellular matrix surrounding renal tubules, only in HUS affected kidneys. Renal sections obtained during the acute stage of HUS demonstrated an increased number of bFGF low affinity bindings sites. To determine the effects of circulating bFGF in normal kidneys, we treated healthy mice with bFGF (15 μg/day ip or vehicle) for 10 days. Transmission electron microscopy studies in bFGF-treated mice demonstrated evidence of renal microvascular endothelial injury, thickening basement membranes and mesangial expansion. Basic FGF (1-10 ng/ml) induced significant proliferation of confluent and subconfluent human mesangial cells and induced contraction of cultured renal microvascular cells. The renal accumulation of bFGF may play an important pathogenic role during the acute stages of HUS and may be one of the mechanisms leading to focal segmental glomerulosclerosis in Argentinean children.