Abstract Setting: It is generally accepted that antibodies do not protect against Mycobacterium tuberculosis infection, as this role relies upon T-cell reactivity. Hence, most studies on antimycobacterial antibodies have been aimed at developing serologic tests, and few explore their role in disease pathogenesis. Objective: To determine the IgG antimycobacterial antibody response of 55 Mexican Totonaca Indians with pulmonary tuberculosis and its correlation with some features of the disease. Design: Study of the profile of antigen recognition by immunoblot and ELISA with isolated antigen 85 complex (Ag85) and whole culture filtrate proteins. Correlation of immunoblot and ELISA results with BCG vaccination, tuberculin reactivity, extent of the disease, clinical setting, and response to treatment. Results: On immunoblot, band reactivity was very poor and the most frequently recognized antigen was the 30-32 kDa, antigen 85 complex (45.8% of serum samples). ELISA with this antigen showed a sensitivity of 72% and a specificity of 100%. Positive antibody titers to Ag85 were observed in 79.4% of patients with non-cavitary tuberculosis (P = 0.012) and in 95.8% of patients who were cured with anti-tuberculosis chemotherapy (P = 0.0001). By contrast, an antibody response to whole culture filtrate antigens had no correlation with the presence of cavitations or with prognosis. Conclusions: Our data show that an antibody response to Ag85, aside from having great potential to develop a serologic test for tuberculosis, was associated with a positive outcome in a cohort of tuberculous Mexican Indians.