SA, an inhibitor of ALA dehydrase, the second enzyme of the heme biosynthetic pathway, has been shown to exert immunosuppressive activity in several systems. When the Walker 256 tumor was grown subcutaneously in outbred Sprague-Dawley rats, SA prevented rejection of the tumor by the host. Human peripheral blood lymphocyte transformation in response to mitogens and antigens in vitro was markedly impaired by addition of SA to the medium. Addition of hematin to the medium did not reverse the SA-mediated inhibition of transformation. This finding suggests that SA may exert immunosuppressive activity by a mechanism separate from inhibition of heme biosynthesis. Continuous administration of SA to Fisher 344 rats profoundly suppressed hemolytic antibody production after immunization with SRBC. Administration of large doses (equivalent to the highest dose of Sa given to tumor-bearing animals) for a month produced a 20% decrease of hemoglobin concentration, a 12% decrease in hematocrit, and no significant effect on leukocyte or erythrocyte concentration. There were no significant changes in tissue histology, including marrow cellularity.