We have previously shown that mice transgenic for a deletion mutant of pNL4-3 have increased bFGF in the extracellular matrix surrounding proliferating renal tubules, microcysts and renal interstitial fibroblast (Kid Int. 46;759, 1994). In the present study we investigated the role of bFGF during renal tubular regeneration, using primary cultures of renal tubular epithelial cells (RTEc) and renal fibroblasts. First, we cultured human RTEc under conditions that did not promote their growth and found that bFGF released into the condition media was one of the major factors increasing the survival of RTEc. Pretreatment of RTEc with heparitinase at a concentration of 0.01 U/ml significantly decreased the binding and mitogenic effects of bFGF on RTEc, suggesting that heparan sulfate proteoglycans (HSPG) present in RTEc are functional bFGF low affinity binding sites. The addition of a reconstituted basement membrane rich in HSPG (matrigel), restored bFGF mitogenic activity. Second, we co-cultured mouse RTEc with renal fibroblasts, and found that bFGF released by RTEc promoted the migration and growth of renal fibroblasts. To test whether a similar effect occurred “in vivo”, bFGF-treated RTEc were injected subcutaneously in BALB/c nu/nu mice in the presence or absence of matrigel. We found that bFGF-treated RTEc, induced the recruitment of “spindle cell fibroblasts”, macrophages and formed transient tumors. The ability of bFGF to increase the adhesion of mononuclear cells to RTEc was confirmed in vitro. Urinary epithelial cells isolated from children undergoing renal injury revealed intense nuclear bFGF staining. Basic FGF stimulated their growth and/or differentiation into tubule-like structures depending on the matrix substrata. Our results suggest that bFGF may have a dual role modulating renal epithelial-mesenchymal interactions. First, it may facilitate renal tubular regeneration by stimulating RTEc survival, growth, differentiation and adhesion of mononuclear cells. Second, bFGF may have a“fibrogenic” effect by stimulating the migration and proliferation of renal fibroblasts.