The present studies were done to clarify potential pathways of the nephrogenic repair process. Media removed from mechanically injured vascular smooth muscle cells and LLC-PK₁ renal tubular epithelial cells significantly stimulated [³H]thymidine uptake and cell number in quiescent LLC-PK₁ cells, demonstrating the existence of potential autocrine and paracrine pathways of nephrogenic repair. The effect of mechanical injury resulting in release of one or more growth factors into culture media was also found in the opossum kidney OK renal tubular cell line. The nonspecific peptide growth factor antagonist suramin inhibited the effect of media from injured LLC-PK₁ cells to stimulate [³H]thymidine uptake in quiescent LLC-PK₁ cells. Exposure of quiescent LLC-PK₁ cells to six growth factors, including acidic and basic fibroblastic growth factors (aFGF and bFGF), platelet-derived growth factors AA and BB (PDGF-AA and PDGF-BB), endothelin-2, and hepatocyte growth factor, reproduced the biological responses seen when quiescent LLC-PK₁ cells were exposed to media from injured cells. Immunoblotting and enzyme-linked immunosorbent assay experiments demonstrated the presence of aFGF, bFGF, and PDGF-BB but not other candidate growth factors in the media from injured LLC-PK₁ cells. A neutralizing antibody directed against bFGF attenuated the effect of media from injured cells to stimulate [³H]thymidine uptake in serum-starved LLC-PK₁ cells. These results demonstrate that mechanical injury to renal tubular epithelial cells results in release of aFGF, bFGF, and PDGF-BB into the media and suggests that bFGF may be involved in an autocrine fashion to promote recovery from injury.