This review illustrates that the 38-kDa protein is one of the most important antigens of Mycobacterium tuberculosis. It is actively secreted but partly attached to the surface of the mycobacterial cell by a lipid tail that may also be responsible for binding of carbohydrate to the protein. It is a major constituent of M. tuberculosis culture fluid after growth on the synthetic Sauton medium and occurs in bacille Calmette-Guérin in far lower concentrations. The protein induces B and T cell responses with high specificity for infection with M. tuberculosis and is a prime candidate for development of new diagnostic reagents for tuberculosis.