Increasing numbers of reports indicate direct effects of ovarian steroids on the central nervous system. Effects of progesterone and its metabolites on brain excitability in humans and in experimental animals have been studied. Anti-epileptic effects have been shown in cats and in women with partial epilepsy and well-defined epileptic foci. The reduced progesterone metabolite 5 alpha-pregnan-3 alpha-ol-20-one and its 5 beta analogue also decreased the epileptic activity resulting from a penicillin-induced cortical focus in cats. 5 alpha-Pregnan-3 alpha-ol-20-one protected mice against metrazol-, bicuculline- and picrotoxin-induced seizures but not against electroshock-and strychnine-induced seizures. Progesterone, 5 alpha-pregnan-3 alpha-ol-20-one and 5 beta-pregnan-3 alpha-ol-20-one also induce anaesthesia in humans and animals; in a rat model of anaesthesia 5 alpha-pregnan-3 alpha-ol-20-one was eight times more potent than methohexitone (the most potent anaesthetic barbiturate). Anaesthesia with loss of the eyelash reflex was observed in humans 75-90 seconds after the intravenous injection of 5 beta-pregnan-3 alpha-ol-20-one in lipid emulsion. The in vivo production and brain distribution of centrally active steroids has also been studied in relation to the phases of the ovarian and menstrual cycle. A subset of women with epilepsy show changes in seizure frequency in relation to hormonal variations during the menstrual cycle. In the luteal phase when progesterone levels are high the number of generalized seizures is low. It is possible that progesterone and its metabolites play a role in epileptic seizures and also in the premenstrual syndrome.