AB S T R A C T Osmoregulation was studied in near term and age-matched Sprague-Dawley rats. Basal plasma osmolality (Posm) and plasma sodium (PNa) were 281+3 mosmol/kg and 134+3 meq/liter, respectively, on the 20th gestational day compared with 292+±3 mosmol/kg and 140+1 meq/liter in virgin animals (P < 0.001), whereas Purea and plasma water content were similar in pregnant and control rats. These differences could not be reproduced in animals receiving progesterone, estrone, or a combination of progesterone and estradiol for 2 wk.Pregnant and control rats were deprived of water for changes (A%) were significantly greater in the gravid animals (P < 0.01). Therefore, Posm was increased without concomitant volume depletion by intraperitoneal hypertonic saline. Again PAVP VS. Posm correlated significantly (r > 0.9; P < 0.001) in each group, and the apparent threshold was 14 mosmol lower in pregnant animals. Diluting ability, tested by oral water loading, was not impaired in the pregnant animals which excreted a 30 ml/kg load as well as controls. Also, chronically hydrated virgin animals whose fluid intake was more than twice that of pregnant rats (for 19 d) did not lower their Posm.In separate studies homozygous Brattleboro rats, which produce no endogenous vasopressin, were also shown to have a decreased Posm (pregnant 292 +4 mosmol/kg; virgin 310+6 mosmol/kg P < 0.001), but unchanged Uosm during pregnancy.Data demonstrate a resetting ofthe osmostat in gravid Sprague-Dawley rats as Posm and the threshold for AVP secretion both decrease significantly during gestation in this species. Studies in homozygous Brattleboro animals with hereditary diabetes insipidus suggest that the osmotic threshold for thirst is reset as well. INTRODUCTION Plasma osmolality decreases during normal human pregnancy to values that range 5-10 mosmol/kg below that of nonpregnant women (1-3). This decrement is apparent by the 6th gestational wk and is sustained until term. If such a reduction in osmolality occurred in a nongravid subject she would cease secreting antidiuretic hormone (ADH)l and enter a state of con-