A skin fibroblast cell strain (GM2995) derived from a patient with xeroderma pigmentosum was received at low passage. As the cells were serially passaged (1:4 dilution), their size and growth characteristics changed. By passage 13, approximately 90% of the colonies produced by cells seeded at low density were composed of small, densely packed cells. Cells capable of anchorage-independent growth were observed after passage 7; they formed round, smooth-edged colonies in soft agar. The frequency of cells exhibiting anchorage-independent growth increased rapidly at subsequent passages, reaching 35-50% of the population by passage 20. This phenomenon was accompanied by the appearance of aneuploidy. These cells are still proliferating actively at passage 35. These late-passage GM2995 cells retain the extreme hypersensitivity to the cytotoxic effect of UV radiation characteristic of early-passage GM2995 cells.