We studied the influence of HLA class I and class II antigens on the suppression of the MLR induced by primed lymphocytes (PLs) alloactivated in vitro. The suppression of 14 different PLs of 83 MLRs was analyzed. The PLs were primed against (i) HLA-DP (SB) (ii) HLA-DR/DQ or (iii) both HLA-DP and DR/DQ. The suppression was analyzed with special reference to the sharing of HLA-antigens between (i) the stimulator in the MLR and (ii) the stimulator generating the PL. HLA-DP and HLA-DR/DQ antigens were equally capable of generating suppressor cells. When these cells were added to MLRs, the specific stimulators induced the strongest suppression (74%), while allogeic cells sharing class II antigens induced a slightly weaker suppression (66%). The suppression related to HLA-DP (60%) was almost identical to that related to HLA-DR/DQ (59%). The HLA-A, B, C related suppression was of the same magnitude (58%). The unspecific suppression (40%), i.e. no relation to known HLA-antigens, was significantly lower than the class II related suppression, but not significantly lower than the class I related suppression. The suppression of the MLR did not seem to be caused by cytotoxic cells, consumption of lymphokines, nor changes in the kinetics of the MLR. Thus, HLA-DP antigens can-like DR/DQ antigens - induce PLs with the ability to suppress the MLR in an HLA-class II (DP or DR/DQ) related, and possibly a class I related, as well as an unspecific fashion.