Somatic cell hybrids were produced by polyethylene glycol-induced cell fusion between metastatic CMT 167 (HGPRT-/OUAR) C57BL/Icrfat mouse lung carcinoma cells and 2 non-metastatic cell lines: C3H/He mouse L-M(TK-) cells of mesenchymal origin and EJ (OUAS) human bladder carcinoma cells. Fusion of 2 different CMT167 (HGPRT-) clones with L-M(TK-) cells followed by selection in HMT medium gave rise to 14 intraspecific hybrids, which were shown to express H-2 antigens specific for both the C57 and C3H mouse strains. Three interspecific hybrids arising from fusion of EJ(OUAS) and CMT167(HGPRT-/OUAR) cells were selected in HMT/ouabain medium and characterized by human isozyme analysis. All the hybrids produced large tumours after subcutaneous inoculation of 5 X 10(5) cells into adult athymic nu/nu mice. The intraspecific hybrid tumours were predominantly sarcomatous (mesenchymal) in structure but a few contained epithelial acini. Metastatic ability (as assessed by production of lung metastases) was completely suppressed in 13 of the 14 mouse/mouse hybrid cell clones. These results suggest that tumorigenicity, tumour structure and the ability to metastasize are expressed independently. The interspecific hybrids, which had not retained a full human chromosome complement, produced metastatic tumours that remained epithelial in structure.