The neuroprotective role of 17beta-estradiol in the hippocampal dentate gyrus of adult rats treated with kainic acid has been investigated. The systemic injection of a single low dose (7 mg/kg) of kainic acid to ovariectomized rats produced a marked loss of Nissl-stained and somatostatin-immunoreactive hilar neurons. A single simultaneous systemic dose of estradiol (150 microg per animal) prevented the kainic acid-induced decrease in Nissl-stained and somatostatinergic hilar neurons. These results indicate that estradiol may protect adult hilar neurons in vivo from neurotoxic-induced cell death.