Sheep peripheral blood mononuclear cells and those depleted of CD8 + T cells and/or monocytes were stimulated with polyclonal mitogens and specific antigens, and analysed by means of cell proliferation assay procedure to examine whether these cell populations are involved in Trypanosoma evansi-induced immunosuppression. The removal of CD8 + T cells failed to normalize the proliferative responses of peripheral blood mononuclear cells from infected sheep to concanavalin A stimulation while the depletion of monocytes resulted in full and enhanced response, showing that macrophages are mainly responsible for the suppression. Although the depletion of CD8 + T cells, monocytes or both restored the responses of the cells to lipopolysaccharide stimulation, the responsiveness of the undepleted cells to this mitogen was significantly higher from day 24 post infection ( p<0.01). The results were discussed in relation to current known mechanisms of depressed lymphocyte proliferation in tsetse-transmitted African trypanosome infections.