During a four-year period, 17 massively obese patients without clinically apparent systemic disease underwent renal biopsy for marked proteinuria. Clinical information and biopsy results were compared with those in 34 normal-body-weight controls matched for age, sex, and similar presentation. Histopathologic changes characteristic of focal glomerulosclerosis were found in nine (53%) of the obese patients and two (6%) of the controls. In addition, five (29%) of the obese patients had occult diabetic nephropathy, while no diabetic changes were seen in controls. Clinically, obese patients resembled controls in most respects. Serum albumin level, however, was higher than in controls (3.5 +/- 0.2 vs 2.5 +/- 0.1 g/dL). Indeed, obese patients with focal glomerulosclerosis had normal serum albumin levels (4.0 +/- 0.1 g/dL). Thus, primary renal disease in massively obese patients with marked proteinuria differed in several important respects from that seen in normal-body-weight patients with a similar degree of proteinuria.