To isolate a variant cell line with increased lymph node metastasising potential from human oral squamous cell carcinoma (SCC) we performed in vivo selection using orthotopic implantation in nude mice. Human oral SCC cells (HSC-3) were injected orthotopically into the tongue of nude mice. After 3 weeks their cervical lymph nodes were excised and the tumour cells metastasised to the lymph nodes were isolated and injected into the tongue of nude mice again, this procedure was performed three times. The resultant cells, designated as HSC-3-M3, metastasised to cervical lymph nodes in 90% of mice, while parental HSC-3 cells metastasised in only 30% of mice after injection into the tongue. HSC-3 and HSC-3-M3 cell lines which have the same origin but different lymphatic metastatic capacities could be a useful model system for studying mechanisms involved in lymph node metastasis of human oral SCC.