To investigate the development of glomerulopathy during the chronic phase of experimental Chagas' disease, C3H-Hej mice were infected with Trypanosoma cruzi trypomastigotes. Deposits of IgG, IgM, and C3 in renal mesangium were observed by immunofluorescence (IF) to increase in size as a function of time after infection (4-6 months). T. cruzi antigens were codeposited in glomeruli with Ig and C3. Electron-dense deposits were visualized in mesangial and paramesangial areas by electron microscopy. Anti-T. cruzi and rheumatoid factor (RF) antibodies (of IgG isotypes) were detected both in serum and in renal eluates. In serum, the titers of both antibodies progressively decreased as a function of time after infection. In renal eluates, titers of anti-T. cruzi antibodies appeared to be stable during the three time periods after infection. By contrast, titers of RF antibodies in renal eluates were shown to increase progressively during these same time periods, paralleling the increase in size of mesangial Ig deposits observed by IF. Several T. cruzi proteins were immunoprecipitated from radiolabeled renal eluates by a control anti-T. cruzi antibody. In addition, antibodies from renal eluates specifically precipitated a 85-kDa protein from radiolabeled T. cruzi lysates, whereas serum antibodies precipitated a broad pattern of T. cruzi proteins. These results demonstrate that mice experimentally infected with T. cruzi can develop a mesangial glomerulopathy during the chronic phase of the disease, which appears to be mediated through immune complexes containing parasite antigens associated with secondary deposition of RF.