Pathologic, clinical and serum complement studies were performed on 18 patients with dense deposit disease (DDD). The patients were divided into 3 groups: group A (10 patients who developed end-stage renal failure within 2.9 +/- 1.0 years of onset) group B (3 patients who developed elevated serum creatinines within 6.8 +/- 4.8 years of onset) and group C (5 patients with no evidence of renal insufficiency after 11.0 +/- 1.4 years of follow-up). Renal biopsies from all patients showed intramembranous, electron-dense deposits in glomerular capillary basement membranes. Most group A and B patients presented with a nephritic and/or nephrotic syndrome and followed an active clinical course. In contrast, group C patients presented with either a nephrotic syndrome or asymptomatic proteinuria +/- hematuria and followed a benign course. Sera from group A and B patients contained reduced concentrations of C3 and factor B and large amounts of C3 nephritic factor (NeF) activity. In contrast, serum of group C patients contained normal amounts of C3 and factor B and low levels of C3 NeF activity. These studies show that some patients with DDD (group C) have a benign illness and that they can be identified by serum levels of C3, factor B and C3 NeF activity.