Latent Trypanosoma cruzi infection may be reactivated in immunosuppressed individuals, with unusual clinical patterns, such as meningoencephalitis, pseudo neoplastic lesions in the central nervous system, and myocarditis with numerous parasites in the heart muscle. To investigate this problem 68 Swiss mice chronically infected with different strains of T. cruzi were treated with different combinations of immunosuppressive drugs (azathioprine, cyclosporine and betamethasone), in such a way as to imitate the situation during post transplantation treatment. Mortality varied from 6 to 25% in treated mice. There were no deaths in untreated controls. Normal mice have been submitted to the same schedules of immunosuppression as controls of treatment and no deaths were registered during treatment. Chronically infected mice showed significant elevation of total number of leukocytes and lymphocytes in comparison with intact controls; a significant decrease in blood leukocytes and lymphocytes occurred post-treatment in two of the treated experimental groups. Exacerbation of myocarditis and myositis and a high incidence of brain lesions, with focal necrosis, granulomatous lesions and glial proliferation even in the absence of parasites were present in immunosuppressed mice but not in infected controls. Although differing in some aspects from Chagas' disease in immunosuppressed humans, the murine model did show some features that resembled it, especially the peculiar pattern of central nervous system involvement.