Human placental tissue contains regulatory molecules that may prevent allo-sensitization. Recently, a 14 kDa beta-galactoside binding protein with demonstrated immunoregulatory properties has been cloned using cDNA from human placenta and expressed in Escherichia coli. The present study assesses the ability of this recombinant immunomodulatory lectin (rIML-1), to prevent experimental autoimmune encephalomyelitis (EAE), a paralytic T cell-mediated disease directed against myelin basic protein (BP). Injection of rIML-1 into Lewis rats inhibited the induction of both clinical and histological signs of EAE, apparently by blocking sensitization of encephalitogenic BP-specific T cells and inducing BP-dependent suppressor cells. Because it is neither immunogenic nor toxic, rIML-1 may have application in humans, and would have distinct advantages over unselective cytotoxic immunosuppressive agents used currently in the treatment of autoimmune diseases and transplantation.