Trypanosoma brucei brucei (T. b. brucei) release a molecule, trypanosome derived lymphocyte triggering factor (TLTF), which stimulates CD8+ cells to produce cytokines and to proliferate. We now report that T. evansi, T.b. gambiense and T.b. rhodesiense also contain factor(s) with similar activity. Thus, homogenates from these parasite taxa triggered mouse or rat lymphoid tissue of mononuclear cells (MNC) to produce interferon gamma (IFN-gamma) and to proliferate. These responses were dependent on CD8 since the activity was blocked by (a) anti CD8 antibodies, (b) occurred in CD8+ but not in CD8- mice and (c) was recorded in human CD8+ but not in CD4+ enriched peripheral blood mononuclear cells (PBL). The presence of TLTF or TLTF-like molecules in the trypanozoan species was also examined by T.b. brucei directed anti-TLTF Mabs using two Mabs with inhibitory activity and one with stimulatory activity. The lymphocyte triggering activity of T.b. gambiense and T.b. rhodesiense, but not T. evansi, was affected by the anti-TLTF Mabs. We conclude that T. evansi, T.b. rhodesiense and T.b. gambiense similar to T.b. brucei, all possess molecule(s) which CD8 dependently trigger lymphocytes. The latter three, related parasite taxa, share TLTF antibody binding epitopes.