Secreted proteins are considered to have an important role in inducing resistance to Mycobacterium tuberculosis infection. We analyzed the proliferation of PBMC from five healthy tuberculin-positive individuals, four tuberculosis patients, and six tuberculin-negative healthy controls to the whole bacilli, the 38- and 10-bDa-secreted antigens, and the 65- and 71-kDa hsp, Comparing the proliferative responses between the two mycobacterial-secreted proteins, we have found that both the 38- and the 10-kDa antigens were recognized by PBMC from healthy tuberculin-positive individuals, However, the magnitude of the proliferation caused by the 10-kDa antigen was significantly higher (P < 0.005) than that with the 38-kDa protein, It was a finding of importance that proliferation to the 10-kDa antigen was comparable to that elicited by the whole bacilli, Characterization of proliferative responses toward the 10-kDa antigen demonstrates that human cells process the 10-kDa antigen prior to its recognition by T cells, and that this process might be through lysosomal pathways, These data confirm the strong T cell response against the M. tuberculosis 10-kDa antigen and demonstrate, for the first time, characterization of cellular activation toward this antigen. The magnitude of the proliferative responses to the 65-kDa hsp in the healthy tuberculin-positive subjects compared with tuberculosis patients was not significantly different (P > 0.01). Finally, PBMC from the healthy tuberculin-positive individuals did not recognize the M. tuberculosis 71-kDa hsp. In summary, human resistant cells to tuberculosis respond to different classes of antigens, including constitutive cell wall proteins, secreted antigens, and hsp. (C) 1995 Academic Press, Inc.