Supernatants from activated leukocyte cultures and individual lymphokines and monokines were added to cultures of JEG-3 human gestational choriocarcinoma cells in vitro, and effects on cell proliferation were measured. Activated leukocyte culture supernatants, recombinant gamma-interferon, tumor necrosis factor, and colony-stimulating factor significantly inhibited JEG-3 proliferation. In contrast, high doses of both interleukin 1 and 2 stimulated JEG-3 proliferation. Low doses of B cell growth factor stimulated JEG-3 proliferation, whereas the highest dose was inhibitory. Further understanding of the effects of lymphokines and monokines on trophoblastic growth may provide important insights into immunologic mechanisms affecting early pregnancy development and tumor-host interactions in gestational trophoblastic neoplasia.