Chlamydia pneumoniae infection is followed by the development of antigen-specific cell-mediated immunity (CMI), which is detectable as a positive lymphocyte proliferation (LP) response to C. pneumoniae elementary body (EB) antigen, but the proteins inducing the T cell activation are not known. In the present work the authors used human T lymphocyte clones (TLC) raised against C. pneumoniae EB antigen to characterize C. pneumoniae proteins as T cell-stimulating antigens. A total of 55% of the TLC established recognized antigenic determinants only on C. pneumoniae species, while the rest of the TLC proliferated to both C. pneumoniae and C. trachomatis EB. The antigen specificity of the TLC was further analysed by stimulating with SDS-PAGE fractionated C. pneumoniae EB proteins. Chlamydia pneumoniae species-specific antigens were found in the molecular weight ranges 92-98, 51-55, 43-46 and 31.5-33 kDa and genus-specific antigens in the ranges 12, 26 and 65-70 kDa. The 46.5-49.5 and 55-61 kDa regions contained both species-specific and genus-specific antigens. Human leucocyte antigen (HLA) restriction analysis for the TLC isolated from an HLA DR4, 15(2) heterozygous person showed the majority (81.3%) to be restricted to the HLA DR4 molecule, the rest being DR15(2)-restricted. An interesting preliminary finding was that the expression of interferon-gamma (IFN-gamma) mRNA by the TLC was predominantly associated with antigen recognition in the context of the HLA DR4 molecule, while interleukin-4 (IL-4) production was linked to antigen recognition in the context of the HLA DR15(2) molecule.