The HLA-restriction specificity of a set of Cytotoxic T-Lymphocytes (CTLs) derived from 20 different individuals and with specificity for antigenic components in Purified Protein Derivative of tuberculin (PPD) were examined against a panel of 50 unrelated target cell donors. PPD pulsed monocytes were used as antigen presenting target cells. CTLs were generated by Interleukin-2 (IL-2) expansion of in vitro PPD activated Peripheral Blood Mononuclear Cells (PBM). The results confirm our previous finding that PPD-specific CTLs are restricted by HLA-class II - and not by class I antigens. The 20 CTLs used together provide reliable cellular typing reagents for the antigens HLA-DR2, -3, -4 and -7 and less so for the antigens HLA-DR1 and -5. In contrast, sharing between CTL- and target cell donors of HLA-DRw6 and -w8 correlates poorly to PPD-specific cytotoxicity. A few consistent exceptional patterns were observed. In one case lack of lysis in spite of HLA-DR antigen sharing could be explained by a split of HLA-DR2 into a normal and a short variant. Positive reactions in combinations, where no HLA-DR antigens are shared, were only few and evenly distributed among CTLs. Thus our findings indicate that our bulk CTLs predominantly contain clones restricted by determinants strongly associated to the serologically defined HLA-DR antigens.