In an attempt to find a parameter for the differentiation of membranous nephropathy with hepatitis B surface antigenemia (HBVMN) and other types of nephrotic syndrome (NS) in HBsAg (+) carriers, we measured the urinary neopterin in 20 HBVMN patients, other types of NS in HBsAg (+) carriers, asymptomatic HBsAg (+) carriers and HBsAg (-) controls, during the active nephrotic phase and in remission. The urinary neopterin excretion was found to be significantly elevated only in the HBVMN during NS or heavy proteinuria. It progressively decreased and corresponded with the amount of proteinuria. In patients with deteriorated renal function, initially, urinary neopterin excretion was significantly higher than in others and it remained significantly elevated during the follow-up period. In vitro when a patient's mononuclear cells were stimulated with lymphoblastoid cell line, the release of neopterin content in supernatant was increased during the acute phase. There was a significant correlation between supernatant and urinary neopterin level. These results suggest that urinary neopterin may be a new biochemical marker for the differential diagnosis of HBVMN and may be used to monitor the course of HBVMN and serve as a prognostic indicator. However, the specificity is not clear.