Effects of progesterone (P) and estradiol-17β benzoate (EB), applied s.c. into sexually mature, long-term ovariectomized (OVX) rats, on subsequent depolarization-induced uptake of Ca 2+ were studied in synaptosomes isolated from the brain stem, mesencephalic reticular formation (MRP), nucleus caudatus putamen (NCP) and the hippocampus. In intact animals, synaptosomal Ca 2+ uptake differed from region to region: it was lowest in the brain stem and highest in the hippocampus. In comparison to intact animals, ovariectomy resulted in a marked increase of the uptake regardless the structure investigated, suggesting an inhibitory action of ovaries on the uptake of Ca 2+ in a considerable portion of rat brain. Single injection of 2 mg P, given to OVX rats 24 h prior to decapitation, evoked a marked decrease in Ca 2+ uptake by synaptosomes of the brain stem and MRF and particularly by those of NCP and the hippocampus. Single injection of 5 μg EB into OVX animals 72 h prior to the experiment was as effective as P in inhibiting Ca 2+ uptake by synaptosomes of the brain stem and MRF, but less effective than P in case of NCP and the hippocampus. This suggests involvement of P and EB in the modulation of synaptic transmission by affecting neuronal Ca 2+ uptake.