Six different cell-mediated lympholysis (CML) combinations were established, four of which generated effector cells against the I-E, and two against the I-A molecule. The cell surface phenotype of effector cells was then determined by depletion of cytotoxic T lymphocyte (CTL) activity with antisera and rabbit complement (C) treatment. Both types of effector cells were completely eliminated by treatment with anti-Thy-1.2 antiserum plus C. Anti-Lyt-1.2 and C depleted anti-A and anti-E killer activity but did not eliminate CTL generated across a whole H-2 difference. One out of three different batches of anti-Lyt-2.2 antiserum did not deplete anti-A killer activity, while it efficiently eliminated CTL generated across the E region or whole H-2 difference. However, two batches of anti-Lyt-2.2 antiserum depleted also anti-A CTL activity. A quantitative difference between anti-A and anti-E CTL in terms of Lyt-2 expression was demonstrated by significant differences in recovery of killer activity, after treatment of these two types of CTL with a wide concentration range of the same anti-Lyt-2.2 antiserum and C. Thus it is concluded that anti-A killer cells have the cell surface phenotype of Thy-1+, Lyt-1, Lyt-2, whereas anti-E CTL are Thy-1+, Lyt-1, Lyt-2. The data are discussed in the context of a possible association of Lyt phenotypes of T cells with the type of MHC antigens they recognize.