Abstract We have evaluated the effect of purified human α-fetoprotein (AFP) on several in vitro correlates of cell-mediated immunity. AFP (100 μg/ml) had no effect on antigen-induced migration inhibitory factor (MIF) production or on the ability of T cells to bind sheep erythrocytes. In contrast, AFP had a twofold effect on mitogen-and antigen-induced lymphocyte proliferation. In a dose-dependent fashion (1–100 μg/ml), AFP was mitogenic to lymphocyte cultures and also suppressed tritiated thymidine incorporation by PHA- and SK-SD-stimulated cultures. Albumin had somewhat similar effects on lymphocyte proliferation but only at 100 μg/ml. The reason for the latter was not clear since the albumin preparation was free of any detectable AFP. Our studies suggest that human AFP may not have any biologically significant immunosuppressive function.