Cultured skin fibroblasts from subjects with cystic fibrosis exhibited normal population doubling times in early passages. After about 13 cumulative population doublings, cystic fibrosis lines doubled more slowly than controls and ceased doubling after about 19 weekly passages. Control lines continued doubling for 27 passages. The premature senescence noted in cells from subjects with cystic fibrosis reconciles controversial observations of cell doubling reported in the literature. Data presented here demonstrate that experiments with cystic fibrosis cells in late passage may generate misleading results since differences from control lines may be ascribed to generalized senile changes rather than to specific results of the cystic fibrosis genotype.