Syrian hamster embryo (SHE) cells were used as a model system to study genetic changes during the rare spontaneous progression from normal to immortalized and then to neoplastically transformed cells. Cultures were established for immortalized and/or neoplastically transformed cells by inoculating 2-5 x 10(5) primary cells into 75 cm2 culture flasks and subsequent subculture at subconfluence. We examined the karyotypic changes in the spontaneously transformed and tumourigenic SHE cells. Chromosome analyses were performed on mitotic cells with the quinacrine banding technique. The primary SHE cell stock (82-6) was karyotypically normal, but cells that had overcome senescence exhibited chromosome abnormalities. More than 90% of cells from passages 18-85 carried the same deletion in the short arm of chromosome 2 (2p-). This deletion was also found in about 70% of cells analysed at passage 15. 2p- was never found in cells at passage 4. We further observed a variety of numeric and structural chromosome changes in addition to 2p-, but these were seen only in transformed cells at high passage numbers and in cell lines derived from nude mice tumours. Our findings suggest that 2p- predisposed SHE cells either to immortalization and/or to progression to tumourigenicity.