We investigated a series of patients with systemic lupus erythematosus (SLE), who had sparse subepithelial and mesangial immune deposits. Our goal was to determine structure: function correlation. We examined whether proteinuria correlated with either capillary wall immune aggregate formation or abnormal podocyte morphology. Renal biopsies from patients with sparse (two or fewer subepithelial or intramembranous electron dense deposits per glomerular capillary loop) immune deposits and podocyte effacement were studied. Patients fulfilled criteria for the diagnosis of SLE. Cases were excluded if the biopsy showed endocapillary proliferation or necrosis. Eighteen biopsies were studied, five from patients with nephrotic range proteinuria (> or =3 g/day) and 13 from patients with non-nephrotic proteinuria (<3 g/day). The five nephrotic patients had a mean foot process effacement of 48% +/- 39% (range 10-100%). Thirteen non-nephrotic patients had a mean foot process effacement of 11.7% +/- 8% (range 0-20%). The only distinguishing morphologic finding associated with nephrotic range proteinuria was diffuse foot process effacement. No correlation between subepithelial deposits and proteinuria was observed. There were no other histologic differences between the nephrotic and non-nephrotic patients. Among these patients, the nephrotic syndrome appears best correlated with podocytopathy rather than subepithelial electron dense deposits, mesangial deposits, or mesangial hypercellularity.