A combination of autoradiographical techniques and computerized image analysis has been used to study the distribution and density of cholecystokinin receptors in the paraventricular and supraoptic nuclei of animals in which the magnocellular-posterior pituitary axis is activated, namely, in salt-loaded (2% sodium chloride) and homozygous Brattleboro rats. [125I]cholecystokinin octapeptide binding was greatly elevated in the paraventricular, supraoptic and accessory nuclei of salt-loaded and homozygous Brattleboro rats, compared to the respective control animals. Furthermore, under these conditions [125I]cholecystokinin octapeptide binding in the paraventricular nucleus was localized almost exclusively to magnocellular subdivisions, and especially to those containing predominantly oxytocin neurons. Autoradiographical competition studies revealed that the increase in [125I]cholecystokinin octapeptide binding in magnocellular nuclei reflected an increase in receptor number (Bmax) rather than affinity (Kd). These results suggest that cholecystokinin receptor density in the paraventricular, supraoptic and accessory magnocellular nuclei is closely linked to magnocellular neurosecretory activity and raises the possibility that cholecystokinin receptors may be involved in oxytocin and vasopressin release processes.