Previous studies have indicated that ribonucleotide reductase may participate in a mechanism of cellular senescence, which involves modifications in deoxyribonucleotide pools, the products of the reductase reaction. Since very little information about the levels of these pools in senescing cells is currently available, an analysis of deoxyribonucleotide levels was carried out in young, old and very old normal human diploid fibroblasts, as well as in a variant human fibroblast strain with an altered replicative life span. These studies indicated that there are marked age-related perturbations in these pools which imply that they may be fundamentally important in a process determining the nonproliferative or senescent state.