The activities of CDP reductase and thymidine kinase in 106to 5 x 106phytohemagglutinin (PHA)-stimulated lymphocytes isolated from 2 to 5 ml of peripheral blood of individual subjects were measured. The activities of CDP reductase (pmol/h/107cells) and thymidine kinase (nmol/h/107cells) were high in infants, 698 ± 307 and 64.2 ± 20.2, constant in subjects of 1–40 years old, 401 ± 181 and 38.1 ± 15.3, and low in persons of more than 80 years old, 121 ± 113 and 22.3 ± 17.8, respectively. The ratio of thymidine kinase to CDP reductase activity increased with age, indicating that dependency on the salvage pathway of DNA synthesis in lymphocytes increased with age. The activities of CDP reductase and thymidine kinase were reduced in patients with the hyperimmunoglobulin E syndrome, congenital cytomegalovirus infection, anhidrotic ectodermal dysplasia with hyperimmunoglobulin A, Bloom's syndrome, immunodeficiency with hyperimmunoglobulinemia, and Down's syndrome. The clinical symptoms of these diseases seem to be due to impaired DNA synthesis of PHA-stimulated lymphocytes, but the degrees of reduction of enzyme activities were generally greater than that of thymidine incorporation in these patients.