Membranous nephropathy (MN) accounts for approximately 10% of all renal lesions of systemic lupus erythematosus (SLE). These membranous lesions often have a clinical presentation similar to that of idiopathic MN and may present before SLE is apparent clinically. However, unlike proliferative lesions of lupus nephritis (LN), membranous LN often does not show a "full-house" pattern of glomerular immunoglobulin and complement (C) deposits by immunofluorescence (IF); only nine of 14 such lesions that we examined stained for all of the following: IgG, IgA, IgM, C3, and C1q. Iskandar et al reported in 1992 that most cases of diffuse proliferative LN showed IgG3 as the major IgG subclass present in glomerular deposits; by contrast, IgG4 predominated in six of seven cases of MN of unspecified etiology. If IgG subclass deposition is similar in membranous and proliferative lesions of LN, then IF staining for IgG3 and IgG4 may be helpful in distinguishing lupus from nonlupus lesions in patients with MN who are lacking a firm diagnosis of SLE. We therefore stained cryostat sections of renal biopsies from 14 patients with SLE and MN (without a proliferative component; World Health Organization [WHO] classes Va and Vb) and 28 non-SLE patients with MN for IgG subclasses by direct IF; the observer was blind to the diagnosis for each case until all were read. The intensity of glomerular staining was graded on a 0 to 4+ scale with increments of 0.5+.(ABSTRACT TRUNCATED AT 250 WORDS)