A 68-year-old male patient with chronic active hepatitis C was treated with interferon-alpha (IFN-alpha) for a period of 5 months. The patient responded well to the IFN therapy showing substantial improvement in liver function and disappearance of HCV-RNA. However, one year after the treatment he was found to have developed proteinuria and showed a reduction in Ccr. Renal biopsy findings were as follows: Light microscopy showed diffuse expansion of mesangial cells with a focal/local increase in cellularity accompanied by capillary loop thickening. Splitting of the basement membrane was also present. An immunofluorescent study showed that IgA was localized predominantly in the peripheral capillary wall. Electron microscopy showed that there was mesangial cell interposition between the peripheral capillary wall and endothelial cells. Furthermore, endothelial cells were expanded and numerous platelets were seen in the capillary lumen. These findings were compatible with focal MPGN accompanied by activation of endothelial cells. These histological data suggest two clinical disease entities: late-onset renal damage induced by IFN-alpha alone, and HCV-induced renal damage possibly modified by the direct effect of IFN-alpha on the endothelium. The present case suggests that IFN therapy for HCV may produce a particular type of renal damage, under the influence of either IFN or HCV infection, and/or both.