Human trophoblast cultures were established from term placentae. Upon exposure to polyriboinosinic-polyribocytidylic acid (poly(I:C] the cultures produced interferon. Results of neutralization experiments and indirect immunofluorescence studies indicated that the trophoblast produces beta-interferon. The fusion of trophoblast cells into syncytia was accompanied by a restriction in interferon release after stimulation with poly(I:C). It was also demonstrated that the malignant choriocarcinoma cell line JAR produced less interferon than the non-transformed cytoorsyncytiotrophoblast.