Lactating rats show reduced oxytocin release compared with virgin female rats in response to a variety of stimuli, including stress and osmotic stimulation. W e sought to establish whether this is a consequence of a reduced response in t h e oxytocin cells, or of a change in stimulus-secretion coupling at t h e level of t h e neurosecretory terminals in the neural lobe. Blood sampling experiments in anaesthetized rats showed that systemic administration of cholecystokinin resulted in significantly less oxytocin release in lactating rats than in virgin female rats. Electrophysiological recordings of single cells in the supraoptic nucleus, however, showed no difference in t h e responsiveness of oxytocin cells to this stimulus. Oxytocin release evoked by electrical stimulation or by depolarization with high potassium solutions was lower in isolated neural lobes from lactating rats than in glands from nonlactating rats, whereas evoked vasopressin release was similar in t h e two groups. The lactating rat neural lobes had a reduced oxytocin content: to study the consequences of depletion we compared hormone release evoked by electrical stimulation in vitro in neural lobes from normal male rats, and from male rats given 2% NaCl to drink for 2 or 4 days. Saline drinking resulted in a reduction in gland content of both oxytocin and vasopressin, and the evoked release of both hormones was also significantly reduced when expressed as a percentage of the gland content, as was also seen for oxytocin release for glands from lactating rats. Finally, measurement of t h e extracellular potassium response to stimulation of the isolated neural lobe as a n index of the excitability of neural lobe neurosecretory axons was unchanged in lactating rats compared with virgin female rats. Together, the data indicate that reduced oxytocin release observed in lactating rats is a simple consequence of reduced oxytocin content in the neural lobe rather than of a reduced excitability of the oxytocin neurons.Lactating rats exhibit a reduced oxytocin release in response to stress ( I , 2) and to osmotic stimulation (2). In addition, electrical stimulation of the region anterior and ventral to the third ventricle (which is essential for normal osmoregulation of oxytocin and vasopressin release; 3, 4). of the paraventricular nucleus, or of the neural lobe itself. all evoke less oxytocin release in lactating rats than in virgin female rats (2). This generalized reduced release of oxytocin appears paradoxical, since it occurs at a time when demand for oxytocin is high; oxytocin release in response to suckling is essential for efficient milk let-down (5-7). The release of oxytocin from the neural lobe of the pituitary is strongly dependent upon the parameters of stimulation, and is optimal in response to brief, high frequency episodes of stimulation similar to the intermittent bursting pattern of oxytocin cell activation observed during suckling (8). Facilitation of oxytocin release with increasing frequency of stimulation is a complex phen...