Hepatocyte growth factor (HGF) is a potent mitogen for tubular cells. Experimental injury to the kidney is associated with HGF release both locally and by distant organs stimulated by circulating ‘injurins’. In this study, the serum HGF concentration was measured in patients with acute renal failure (ARF). Normal subjects and chronic renal failure patients either not on dialysis or on regular dialysis treatment served as controls. Human mesangial cells were incubated with sera from ARF patients and controls. The serum HGF concentration was strikingly increased in ARF patients (478 ± 68 ng/dl) and was normal in chronic renal failure patients not on dialysis (20 ± 3 ng/dl) and in those on regular dialysis treatment (25 ± 3 ng/dl). Serum of ARF patients strongly stimulated HGF release from mesangial cells (1,384 ± 55 ng/ml) in comparison with normal serum (67 ± 10 ng/ml). These results indicate that in ARF HGF participates in tubular repair both as an endocrine factor, released in the circulation, and as a paracrine substance, diffusing to the tubules from the mesangium.