Patients with diabetes mellitus (DM) are more susceptible to bacterial infection including pulmonary tuberculosis. To define the immunopathologic mechanisms underlying pulmonary tuberculosis in patients with DM, the production of IFN-gamma by CD4+ T cells or PBMC were followed up longitudinally during antituberculous chemotherapy. At the time of diagnosis, IFN-gamma production by CD4+ T cells in either tuberculosis patients without DM (TB) or with DM was significantly lower than that in the healthy control. CD4+ T cells in tuberculosis patients with DM under poor control (DM(p)TB) produced significantly less IFN-gamma than did patients with DM under good control (DM(g)TB). In longitudinal studies, IFN-gamma production in both TB and DM(g)TB patients returned to the control level by 6 months, whereas the production in DM(p)TB patients remained depressed. There was no significant relation between regimens of antituberculous chemotherapy and the production of IFN-gamma by PBMC in all subject groups. IFN-gamma production was depressed in DM(p)TB patients treated with HREZ for 6 months. These results indicate that depressed production of IFN-gamma in DM(p)TB patients is prolonged not due to tuberculous infection but intrinsic defect presumably induced by poorly controlled DM.