One crucial step in tumor metastasis is detachment of cells from the primary lesion. This involves down-regulation of homophilic binding intercellular adhesion molecules. To determine whether this occurs in metastasis of human small-cell lung cancer to lymph nodes, we examined expression of E-cadherin, carcinoembryonic antigen (CEA), and neural cell adhesion molecule (NACM) on cells from patients with small-cell lung cancer, some cells were obtained from primary lesions and others from lymph-node metastases. Cells in all of the five lines from primary lesions expressed E-cadherin, unlike those in all of the five lines from lymph-node metastases. Cells in all of the five lines from primary lesions expressed CEA, as did those in only one of the five cell lines from lymph-node metastases. Cells in lines from primary and metastatic lesions did not differ in the expression of NCAM (4/5 positive). Expression of E-cadherin and of CEA were closely correlated. Because E-cadherin and CEA are involved in the binding of epithelial cells, these findings demonstrate that metastasis of small-cell lung cancer to lymph nodes is associated with a lack of the epithelial intercellular adhesion molecules E-cadherin and CEA. The expression of these molecules is involved in the metastasis of small-cell lung cancer to lymph nodes.