We have investigated the comparative effects of estradiol benzoate (EB), the antiestrogen clomiphene citrate (CC), and the progestin medroxyprogesterone acetate (MPA) on seizures induced by systemic injection of kainic acid (15 mg/kg i.p.) in male and female rats. Subcutaneous administration for 10 days of EB (10 micrograms/kg) or high doses of CC (50 mg/kg) significantly potentiated kainate-induced seizures, with this effect being more pronounced in male animals. Doses of 2.5 mg/kg of CC potentiated kainate-induced seizures in male rats but were ineffective in female rats. Low doses of CC (0.5 mg/kg) exhibited a mild anticonvulsant effect in both sexes. Repeated administration of MPA (2.5 mg/kg) partially protected female animals against kainate-induced seizures; in male animals, MPA induced a 30% increase in the seizure severity score, although the difference from the score of control male rats was not significant. These data suggest that sex steroids influence kainate-induced seizures in a sex-dependent manner and that the effects of the antiestrogen CC are dose dependent. This should be taken into account in view of a possible use of CC and MPA in hormonal therapy for seizure disorders.