The effect of peripheral hypertonic stimulation on the neurons of hypothalamic paraventricular nucleus (PVN) was investigated in the present study with both electrophysiological and immunocytochemical methods. The discharge frequency of the neurons with phasic activity in PVN could be increased by intraperitoneal (i.p.) injection of hypertonic saline (HS, 1.5M NaCl) (from 2.8 +/- 0.5 Hz to 5.4 +/- 0.9 Hz, P<0.001). The Fos expression in PVN could be enhanced (from 21.2 +/- 12.9 to 217.3 +/- 38.5 Fos-positive neurons, P<0.001) by i.p. HS and the majority of AVP-positive neurons expressing Fos (91.7 +/- 3.6%) was in magnocellular subdivision of PVN. After intracerebroventricular (i.c.v.) injection of losartan, angiotensin II type 1 (AT1) receptor antagonist (5 microg/microl), the excitatory effect of peripheral hypertonic stimulation on PVN neurons with phasic activity was inhibited significantly, and the number of the neurons co-expressing Fos and AVP in PVN decreased significantly (P<0.001) as well. The result demonstrated that the vasopressinergic neurons in PVN could be excited by peripheral hypertonic stimulation, and this excitation might be mediated by angiotensin II fibers projecting from subfornical organ to PVN.