Demonstration of Mycobacterium tuberculosis in a smear or culture is the most reliable method for diagnosing tuberculosis (TB). In the last 10 years, several enzyme-linked immunosorbent assays (ELISAs) based on mycobacterial antigens (such as antigen 60, 38 kDa antigen, and antigen Kp90) have been used for the rapid diagnosis of TB. In this study, we report the isolation of an immunodominant lipopolysaccharide (LPS) antigen from M. tuberculosis H(37)Rv, which can be used for the serodiagnosis of TB. The LPS antigen was compared with three commercially available mycobacterium-specific antigens for the detection of TB. The antigens were evaluated using serum samples obtained from 59 Indian patients (19 patients with active pulmonary TB, 20 with extrapulmonary TB, and 20 with nontuberculous pulmonary disease) and 20 healthy adults. Antigen 60 IgG (sensitivity 89%, specificity 97%) and LPS (sensitivity 84%, specificity 97%) were more sensitive and specific than 38 kDa antigen IgG (sensitivity 79%, specificity 97%) and Kp90 IgA (sensitivity 82%, specificity 40%). These results indicate that the LPS antigen can be used as a sensitive tool for the serodiagnosis of TB and could be utilized to develop an ELISA for the screening of patients for TB.