We compared the clinicopathologic features of 22 patients with hepatitis B virus-related membranous nephropathy, all with detectable glomerular hepatitis B e antigen, and of 26 patients with lupus nephritis class V. Both groups of patients similarly presented with heavy proteinuria or nephrotic syndrome; however, the patients with hepatitis B virus-related membranous nephropathy, who were predominantly male, did not have the extrarenal manifestations and autoantibodies seen in systemic lupus erythematosus. The glomerular lesions in both clinical entities were similar and at times indistinguishable, demonstrating polyclonal immunoglobulins and polytypic complements in similar subepithelial ultrastructural distribution. No morphologic feature, single or combined, carrying a high positive predictive value for the diagnosis of either nephritis was identified. Lesions such as hematoxyphil bodies and fingerprint dense deposits, distinctive of systemic lupus erythematosus, were rarely found. At the time of biopsy, when systemic lupus erythematosus is not clinically suspected, the diagnosis between hepatitis B virus-related membranous nephropathy and lupus nephritis may be difficult or impossible to differentiate, especially in geographic areas where both lupus nephritis and hepatitis B surface antigen carriers are common. This study focused on the use of specific monoclonal antisera to detect glomerular hepatitis B virus antigens, which contribute to the diagnosis of hepatitis B virus-related nephritis.