Two secreted antigens (38 and 30 kDa) and 1 cytosolic antigen (16 kDa) were purified in our laboratory from Mycobacterium tuberculosis culture filtrate and cytosol using chromatographic/electrophoretic methods. One recombinant antigen (27 kDa, MPT51) expressed in Escherichia coli was also isolated. All the 4 antigens were tested individually for detection of serum IgG, IgA, and IgM (a total of 476 sera from 5 groups) by indirect enzyme-linked immunosorbent assay. Keeping the well-reported 38 kDa as the main candidate, the usefulness of the other antigens, which may add to the test positivity in cases not diagnosed by 38 kDa, was analyzed. The individual antigens ranged in their sensitivity from 57% to 67% (IgG). Addition of other antigen results, with that of 38 kDa, offered a sensitivity of 91% in smear- and culture-positive tuberculosis (TB), 78% in smear-negative culture-confirmed TB, and 97% specificity in normal healthy subjects. IgG antibody to multiple antigens (38, 30, and 16 kDa) may be a sensitive, specific, rapid, and cost-effective test to rule-in clinical suspicion of pulmonary TB.