A series of mouse monoclonal antibodies (mAb) to human differentiation antigens known to have agonistic activity for human T or B cells was found to bind specifically to macaque T or B cell subsets. Most of these mAb also stimulated macaque lymphocyte proliferation, implying that they recognize functional homologues in monkeys. Anti-CD3, anti-CD28 (9.3), and anti-Lp220 (CD45R) mAb stimulated proliferation of both human and macaque T cells; similarly, anti-IgM and anti-CDw40 mAb stimulated both human and macaque B cells. In contrast, anti-CD20 and anti-CD39 mAb, which are known to stimulate human B cells, did not stimulate macaque B cells. A human low-molecular weight B cell growth factor (BCGF) and anti-IgM were co-stimulatory for macaque splenic B cells but not for blood B cells, suggesting that B cell subpopulations may differ in their responsiveness to BCGF. The results show that functional epitopes on some lymphocyte surface molecules such as CD28 or CDw40 are conserved in primate evolution. Functional epitopes on other cell surface molecules such as CD3 and CD20 may have more complex evolutionary constraints.