The antiaggressive effects of progesterone (P) were evaluated in association with alterations in [35S]t-butylbicyclophosphorothionate (TBPS; chloride ion channel antagonists) binding in some forebrain sites of the female rat using in vitro quantitative autoradiography. The administration of 4 mg P was followed by a reduction in the frequency of different aggressive behaviors such as circling, nose-to-nose and fighting (mostly of the defensive nature) in ovariectomized (OVX) sexually mature rats, housed in pairs, during male-female encounters. Quantitative autoradiography data revealed that the same P dose, at the forebrain level, was responsible for low [35S] t-butylbicyclophosphorothionate binding levels in the medial preoptic area, lateral and basolateral amygdala nucleus and oriens-pyramidalis hippocampus CA1 layer, with even lower values being obtained following the in vitro addition of the potent P metabolite 5 α-pregnan-3 α-ol-20-one. These results suggest that the probable antiaggressive role of P during heterosexual encounters may be regulated by a local potent metabolite acting at the membrane site of the GABA complex. © 1990.