The role of carcinoembryonic antigen (CEA) in metastasis was examined using Chinese hamster ovary (CHO) cells which had been transfected with cDNA encoding CEA. When 2x10(6) cells of a clone of CEA-expressing transfectants, designated CHO/CEA, were injected intrasplenically into athymic nude mice, 8 out of 8 mice developed liver metastases. In contrast, a vector-transfectant C5 did not at all form metastasis in the assay (0 of 8). There was no difference in growth rate between CHO/CEA and C5 in vivo as well as in vitro. MoAbs to N-domain of CEA markedly inhibited the liver metastasis of CHO/CEA cells, while a MoAb to domain III of the antigen did not. These findings suggest that CEA may play an important role in hepatic metastasis, and that the N-domain of CEA molecule contributes to the function of CEA in metastasis. (C) 1994 Academic Press, Inc.