Variant sublines LMF3, LMF4 and LMF5 with high metastatic potential were established from a human oral squamous carcinoma cell line HSC-3. These sublines metastasized to the draining lymph nodes after subcutaneous inoculation into nude mice. They were obtained by sequential selection in vivo from the parent HSC-3. At each step, the cells which metastasized to lymph nodes were cultured and reinoculated into nude mice. Two other cell lines HSC-2 and HSC-4 were also established from other patients, that had neither invasive nor metastatic potential. Biologic properties were compared among high metastatic, low metastatic and non-metastatic cells. Metastatic cells grew rapidly and invaded into surrounding tissues at the inoculated site. The incidence of pulmonary colonization after intravenous injection of tumor cells was high in selected variants. Metastatic cells formed diffuse colonies in type I collagen matrix and had a higher tendency to adhere to type IV collagen network.