Polyclonal activation of lymphocytes and immune complex-mediated glomerular lesions were induced in C57Bl/6 mice by injecting bacterial lipopolysaccharide (LPS) twice a week for 2 weeks. The usefulness of such a model for in vivo evaluation of immunomodulatory and therapeutic effects of drugs, was investigated by treating mice with DIAM4, a cyclophosphazenic compound known to modulate polyclonal activation of lymphocytes and to prevent mouse lupus nephritis. Prevention of LPS-triggered lymphocyte polyclonal activation and glomerular lesions was observed in the DIAM4-treated mice. Such a model can be used conveniently to select compounds effective in the treatment of immune glomerulonephritis.