The acute effects of 17 beta-estradiol on brain excitability were studied in vitro and in vivo utilizing rat hippocampal slices and a cat cerveau isolé preparation. The hippocampal slices were perfused with 17 beta-estradiol (10(-7)-10(-10) M) for 30 min. No effects were observed on synaptic activation and inhibition and on the response to iontophoretically applied GABA in intact and ovariectomized female rats (n = 43). In males (n = 32), however, a small (12%) but significant increase in population spike amplitude was observed after 30 min exposure to 10(-9) M 17 beta-estradiol. Higher and lower concentrations were ineffective. In vivo, no acute effects of 17 beta-estradiol on focal epileptic seizure thresholds, evoked potentials, or augmenting response were observed in the visual cortex of non-estrous female cats (n = 11; median dose 1 micrograms/kg, range 0.5 microgram/kg-10 mg/kg).