Although estrogen has been considered as a sex hormone for decades, recent reports suggest that estrogen might modulate the development and physiological function of the brain. In addition, the subcellular localization of estrogen receptors (ERs) has shown their presence within both the perinuclear cytoplasm and nuclei, suggesting that these ERs may differ functionally. We, therefore, assayed changes in the subcellular localization of ER-alpha immunoreactivity (IR) in rat pheochromocytoma PC12 cells during the artificial senescence induced by the telomerase inhibitor, 3'-azido-3'-deoxythymidine (AZT). After 2 months of culture with AZT, PC12 cells showed morphological and biochemical characteristics of cellular senescence. In the cells showing artificial senescence, the ER-alpha IR was mainly localized within the cytoplasm, whereas in control cells, ER-alpha IR was found only in the nuclei. Since senescence was induced by AZT, which inhibits the action of telomerase whenever the cells divide, the change in subcellular distribution of ER-alpha IR may be correlated with the length of the telomere.