12-O-tetradecanoylphorbol-13-acetate (TPA) is a potent tumor promoter which can modulate the proliferative response of bovine lymphocytes in culture. TPA acts as a co-mitogen when added to cells simultaneously with the lectins phytohemagglutinin (PHA) or Concanavalin A (ConA). In contrast, pretreatment of cells with TPA derpresses the response of the lymphocytes to lectins and blocks the mixed lymphocyte response (MLR). The inhibition is reversible. We have evidence that TPA acts indirectly through production of suppressor cells and possibly soluble factor(s) to mediate its activity. We propose to separate the cells which are responsive to TPA and to determine if they cause suppression of other cells in culture. Experiments involving selective killing as well as physical separation will be performed. TPA-treated cells as well as their culture media will be tested for their effect on the response of untreated cells to lectins and to allogeneic cells. If a specific class of cells can be separated we will try to identify it and to determine if it produces a soluble inhibitory factor. The factor would be compared with some known lymphokines and products of other TPA-treated cells. Some other tumor promoters related to TPA will be tested in the lymphocyte system to determine the correlation between tumor promotion in vivo and lymphocyte inhibition in vitro.