This study describes the effects of cytokine peptides released into the supernatant during an early allogeneic reaction (AR) of mouse spleen lymphocytes or brain cortex cells which differ in their major histocompatibility complex (MHC). The peptides were isolated by ultrafiltration, liquid chromatography and HPLC. We found that both peptides stimulated the cell surface Na+,K+-ATPase and Ca2+-ATPase activities of quiescent spleen lymphocytes in vitro and mimicked early allogeneic cell interactions. Both brain and spleen AR peptides inhibited Concanavalin A-stimulated spleen lymphocyte proliferation, whereas 3H-TdR incorporation into DNA of the E7 neuroblastoma cell Une was stimulated by these peptides. The peptide isolated from the supernatant of the allogeneic brain ceU reaction inhibited phagocytosis in phorbol myristate-stimulated LA5-9/8 mouse macrophage cell line. Immunosuppressive activity of spleen AR peptide is supported by inhibition of spontaneous E rosette formation by lymphocytes. The immunosuppressive effect of isolated peptide cytokines on lectin-activated lymphocytes was comparable with the serum thymic factor (FTS, Lenfant et al. 1983). These changes demonstrate the pleiotropic cytokine actions mediated by plasma membrane of immune system and brain cells.