SUMMARYBALB/c and C57BL mice were kept for prolonged periods on immunosuppressive treatment combined with persistent antigenic stimulation. Azathioprine (Imuran; Burroughs Wellcome) or antilymphocyte serum was used as an immunosuppressant, and lactic dehydrogenase elevating virus (LDV), vaccinia virus (VAC), complete Freund's adjuvant (TB; Difco), or HeLa cells were used as antigens. Control mice were untreated or were kept on immunosuppression or antigenic stimulation alone. Malignant lymphoblastic lymphomas developed in 20% of BALB/c mice treated with azathioprine and antigens. No lymphomas were observed in control mice. Immature plasmacytoses developed in 40% of BALB/c and in 27% of C57BL mice when they were treated with antilymphocyte serum (ALS), with or without antigenic stimulation. In addition, chronic ALS administration led to membranous glomerulitis and glomerulonephrosis in 8% of all treated mice, the changes being most severe in antigenically challenged animals. Lymphoma development is interpreted as a direct result of persistent antigenic stimulation in immunosuppressed mice, and a possible pathogenic mechanism is discussed. The renal lesions are thought to be caused by circulating antigen-antibody complexes.