We investigated the immunoregulatory properties of a recently described inhibitor of lymphocyte proliferation, suppressin (SPN). It was determined that preincubation of murine leukocytes with SPN enhances natural killer cell (NK) activity. In addition, SPN potentiates interferon-γ (IFN-γ) augmentation of NK activity. Furthermore, preincubation of murine leukocytes with SPN induces the production of IFN-α/β. The IFN-α/β produced is active in NK assays as well as vesicular stomatitis virus neutralization assays. In vivo, SPN increases the time of survival of C57BL/6 mice injected with EL-4 lymphoma cells. Interestingly, SPN inhibits immunoglobulin (IgA, IgG, and IgM) production in response to the mitogen, concanavalin A in a dose-dependent manner. Collectively, the above data indicate SPN may have numerous applications in clinical science including tumor surveillance and autoimmune diseases such as arthritis. © 1990.