Freeze-fracture replicas of hypothalamic arcuate neurons and of Purkinje and granule cells of the cerebellar cortex from adult female rats were assessed in order to test the possible influence of estradiol on nuclear pores. Rats were ovariectomized and injected either with estradiol or with vehicle. An additional group of rats in proestrus was also studied. Pore diameter was not affected by ovariectomy or estrogen treatment. In arcuate neurons, the number of nuclear pores per nuclear membrane area, the total number of pores per nucleus, and the percentage of nuclear pores arranged in clusters were decreased by ovariectomy and increased within 30 minutes after estradiol administration to ovariectomized rats. The effect of estradiol on nuclear pores was sustained for several days; the number of pores and the percentage of pores in clusters reverted to control values by 1 month after the hormonal treatment. None of the above mentioned changes was observed in Purkinje and granule cells of the cerebellar cortex. These results indicate that estradiol may modulate the number and distribution of nuclear pores in arcuate neurons and suggest that the modification of the ultrastructure of the nuclear envelope may be one of the first effects of gonadal steroids on target cells.