The hypothalamic supraoptic (SON) and paraventricular nuclei (PVN), median eminences (ME) and neural lobes (NL) of normally hydrated control rats (group 1), and of rats drinking 2% NaCl for 7 (group 2), 30 (group 3) or 90 days (group 4) were investigated using immunohistochemistry for neurophysins (NP), arginine vasopressin (AVP) or oxytocin (OXY). Animals from the 3 experimental groups showed equivalent decreased levels of immunoreactive NP in the SON and PVN, but the greatest decrease was in the SON. Dendrites of SON and PVN neurons became loaded progressively with immunoreactive NP, AVP and OXY as salt loading proceeded. In rats of group 2, axons leaving the SON and PVN showed a marked depletion of immunoreactive material. The latter was found mainly at the periphery of widely spaced axonal swellings, clearly contrasting with the small and narrowly spaced beads of the neurosecretory axons of control rats. In rats of groups 3 and 4, axons leaving the SON and PVN resembled those of control rats. In the ME of the animals in all experimental groups, the same degree of decrease of immunoreactive NP was observed. In rats of group 3, bundles of axons containing immunoreactive AVP and OXY frequently projected through the ependymal lining of the ME into the third ventricle. In the NL of all experimental animals, a marked decrease occurred in the amount of immunoreactive NP, AVP and OXY. The decrease of immunoreactive AVP, however, was more pronounced in rats of group 2 than in those of groups 3 and 4. The NL of rats in group 4 were approximately 80% larger than those of control rats.(ABSTRACT TRUNCATED AT 250 WORDS)