Aiming at the production of anti HLA--DR test sera, eight healthy human volunteers were immunized by repeated intradermal injections of lymphocytes which were selected to be incompatible for one HLA--DR antigen, and matched as well as possible for HLA--A,--B,--C antigens. One out of 3 recipients immunized exclusively against HLA--DR produced lymphocytotoxic HLA-DR antibodies. The remaining 5 recipients were immunized against 1 or more HLA--A,--B,--C antigens in addition to one HLA--DR antigen. After 3 immunizations, 3 of these reacted with strong HLA--A or --B antibody production; however, only one showed a parallel anti HLA-DR antibody response detectable by complement dependent lymphocytotoxicity. Testing of the recipient sera in the antibody dependent cell-mediated cytotoxicity (ADCC) assay revealed that 6 of the 8 recipients did react early to the immunizations with HLA specific antibody production. However, in spite of repeated booster injections it was not possible to obtain more than the above-mentioned 2 sera with HLA--DR antibodies strong enough to react in the lymphocytotoxicity microtechnique.