Abstract A sensitive and specific radioimmunoassay was used to measure plasma antidiuretic hormone (plasma arginine vasopressin, P AVP) concentrations in a conscious desert-adapted mammal, the banner-tailed kangaroo rat ( Dipodomys spectabilis; 131 ± 2.3 g body mass), during normal hydration and in response to progressive dehydration. Simultaneous measurements of P AVP and plasma osmolality (P OSM) in these experiments permitted determination of the hypothalamo-neurohypophyseal system-osmoreceptor set point and sensitivity to extracellular hyperosmolality during dehydration. In normally hydrated kangaroo rats, acclimated to room temperature (20–24°) and fed a dry grain diet, P OSM and P AVP averaged 308.6 ± 0.7 mosmol/kg H 2O and 6.0 ± 0.7 pg/ml (2.2 ± 0.2 μU/ml), respectively (means ± SE). In separate groups of animals subjected to 48, 96, 144, or 192 hr of dehydration, P OSM and P AVP increased in a parallel linear manner with time to maxima of 329.7 ± 2.4 mosmol/kg H 2O and 68.8 ± 4.4 pg/ml (24.9 ± 1.6 μU/ml), respectively, at 192 hr of dehydration. Thus, a highly correlated and significant relationship between P OSM and P AVP ( r 2 = 0.941, P < 0.001) exists in dehydrated kangaroo rats, quantitatively defined by the linear regression equation P AVP (pg/ml) = 2.99 (P OSM − 306.4), with an apparent osmotic threshold for AVP release at a P OSM of 306.4 mosmol/kg H 2O. In comparison with previous radioimmunoassay studies on the osmotic regulation of P AVP in various mammalian species, the present studies indicate that (1) during normal hydration, the kangaroo rat maintains an elevated P OSM and a basal P AVP that is two- to threefold higher than that of the laboratory rat or other mammalian species; and (2) during dehydration, the kangaroo rat exhibits a markedly elevated osmotic sensitivity for AVP release and an enhanced capacity to increase and maintain P AVP for prolonged periods of time, achieving P AVP two- to threefold higher than the laboratory rat (a nondesert rodent of similar body mass).