The effect of central osmotic stimulation on oxytocin (OT) secretion from the paraventricular nucleus (PVN) was examined using a newly developed in vivo microdialysis technique. A dialysis probe was inserted into the PVN region and microdialysis was performed in conscious animals. Hyperosmotic solutions were delivered via the dialysis probe, and perfusate and blood samples were collected. OT was consistently detected in the PVN dialysate. Hyperosmotic sodium chloride (1 M) produced a significant increase in dialysate and plasma OT, whereas D-mannitol (2 M) had no effect. These results suggest that (1) in vivo microdialysis may provide a useful technique for the evaluation of neuropeptide secretion from specific brain regions and (2) there are sodium-sensitive cells in the PVN region which respond to increases in extracellular sodium, resulting in an increase in central and peripheral oxytocin secretion.