Monoclonal antibodies (Mabs) raised against Mycobacterium leprae sonicate defined two different determinants on related, cell-wall-associated, carbohydrate antigens common to M. leprae, M. bovis (BCG), and M. tuberculosis. Antigen inhibition ELISA and antigen capture assays demonstrated that the two antigens were present in a cell-wall fraction, M. leprae resonicate. There was species variation in the distribution of the antigens; the 4.5-6 kD antigen was more abundant in M. tuberculosis and M. bovis, while the 30-40 kD antigen was more concentrated in M. leprae preparations. Although both were present in the cell wall, only determinants on the 30-40 kD antigen were accessible on intact bacilli. The results from capture assays and Mab affinity chromatography with both L9 and L4 indicated that the 4.5-6 kD antigen was probably a fragment of the larger molecule. Both antigens are significant immunogens in the human B-cell response to M. leprae.