Monoclonal anti-Lyt-1 (alpha Lyt-1) and alpha Lyt-2 manifest inverse effects on allogeneic mixed lymphocyte reactions when added to the reaction mixtures without complement. alpha Lyt-1 augments cell proliferation and generation of cytotoxic cells but has no effect on cell-mediated cytolysis, whereas alpha Lyt-2 blocks cell proliferation, generation of killer cells, and cytolytic activity of killer cells. The augmenting effect of alpha Lyt-1 cannot be attributed to a direct mitogenic effect on T cells. Both inhibition by alpha Lyt-2 and potentiated by alpha Lyt-1 require interaction of responder cells with the antibodies during the first 24 hr of the mixed lymphocyte reaction, indicating that early stages of the reaction are sensitive to Lyt antibodies. The enhancing effect of alpha Lyt-1 on alloantigen-induced T-cell proliferation is associated with augmented production of T-cell growth factors. When alpha Lyt-1 is present in mixed lymphocyte cultures, the supernatant media collected after 24 or 48 hr of culture induce higher proliferation of activated T cells compared to media of mixed lymphocyte cultures incubated in the absence of antibodies or in the presence of alpha Lyt-2 which has no effect on secretion of growth factors. The differences in the effects of alpha Lyt-1 and alpha Lyt-2 could not be attributed to differences in heavy chain constant region functions because both were of the same lambda 2A immunoglobulin class and were used at the same concentration. The data suggest a possible role for Lyt-1 molecules in early activation and mitogenesis processes such as production of growth factors.