Fetuin, the bovine alpha-fetoprotein, contains glycopeptide sequences similar to those found on red cells. As a result, it is capable of strong physical interaction with the phytohemagglutinin isomitogens (H-PHAP) which possess two or more R (red cell binding) subunits as part of their tetrameric structures. Fetuin shows little or no interaction with L-PHAP, a phytohemagglutinin made up of four L subunits which also lack red cell affinity. Despite these differences fetuin is able to inhibit both H- and L-PHAP-induced lymphocyte transformation and is also capable of inhibiting the mitogenic effects of pokeweed mitogen, concanavalin A, antithymocyte antiserum, and the one-way mixed lymphocyte culture. In the case of L-PHAP, the inhibitory effect of fetuin is proportional to the intensity of the mitogenic stimulus. The inhibitory effects of fetuin upon lymphocyte transformation may result from perturbation or "blindfolding" of the cell membrane in a manner analogous to other immunosuppressive serum alpha-globulins. Alpha-Fetoproteins may play an immunoregulatory role during fetal development.