The effects of an onco-fetal hormone, hCG, were tested on replication of Nb 2 node rat lymphoma cells, which have previously been shown to be responsive to lactogenic hormone stimulation. Cells were maintained in suspension culture in Ham's F-10 medium containing horse serum (15%) and fetal calf serum (2.5%). Forty-eight hours before experiments, medium was replaced with horse serum (10%) only. In the absence of added hCG, cell doubling time was about 24 h. Purified hCG preparations (CR 119) and the Second International Standard for hCG (WHO) stimulated lymphoma cell replication after 72 h of exposure to the cells. The stimulation was dose dependent, beginning at 100 pg/ml and peaking at 10 ng/ml (140% vs. controls, P less than 0.001). Specific hCG antiserum (SB6) did not alter cell replication, but when added simultaneously with hCG, completely blocked the stimulation induced by hCG (10 ng/ml). No effect on cell proliferation was seen when the beta-subunit of hCG, the common glycoprotein alpha-subunit, human LH, FSH, or placental lactogen was added to the cells. These results indicate that hCG can stimulate proliferation of rat lymphoma cells in vitro. If hCG affects human tumors in a similar fashion, the ectopic production of the hormone by tumors may stimulate growth of the neoplasm.