A gradual decrease in colony-forming ability of human fibroblast strains was found to be an early sign of cellular senescence. This decrease occurs in fibroblast strains from patients with ataxia-telangiectasia (A-T) at significantly earlier passage levels than with normal strains; accordingly, the lifespan of A-T cells in culture is shorter than that of normal strains. The colony-forming efficiency of A-T cells can serve as a quantitative measure for serum quality: A-T cells fail to form colonies, or have a markedly reduced colony-forming efficiency, in some batches of calf serum and newborn calf serum, whereas in other batches their clonal growth is maximal. Normal fibroblasts show the same colony-forming efficiency with all batches of serum. Fibroblast growth factor (FGF) and epidermal growth factor (EOF), but not insulin, were able to correct this deficiency in the growth-promoting ability of certain serum batches. In addition, conditioning medium containing these sera on confluent unirradiated or irradiated monolayers of any other human fibroblast strain had the same effect. A-T cells seem to have an increased demand for certain FGF- or EGF-like growth factors that are present in variable amounts in different serum batches and also in conditioned medium.