NAD levels markedly increase upon mitogen stimulation of lymphocytes from young subjects. In contrast, lymphocytes from old subjects do not increase NAD levels upon stimulation. A survey of 35 individuals aged 18-79 years revealed a significant age-dependent decrease in the NAD response to mitogen stimulation. No significant differences were noted in lymphocytes from age-matched individuals with Down's syndrome or diabetes mellitus. On the other hand, cultured skin fibroblasts showed elevated NAD levels with age. However, this effect appears to be due to increased size of the cells since the NAD/protein ratio is unchanged. Skin fibroblasts from patients with progeria exhibit much higher levels of NAD and protein per cell than age-matched controls.