Rats were injected with vasopressin tannate in oil twice daily for 80 days and aqueous vasopressin every 4 hours for the next 3 days. During vasopressin administration, spontaneous water imbibition was less than and serum osmolality remained the same as that of controls receiving peanut oil. After 80 days, renal response to vasopressin was still normal. Beginning 4 hours after vasopressin was stopped, rats were subjected to a 3-day period of water deprivation during which there was no significant difference between previously vasopressin-treated and control rats with respect to: a) urine volume and urine osmolality measured at 12-hour intervals; b) weight loss; c) rise in serum osmolality. No polydipsia developed during 4 weeks after vasopressin was discontinued. It is concluded that prolonged administration of vasopressin to rats does not cause even transient subsequent impairment of water conservation mechanisms including neurohypophyseal release of ADH. This may imply that regulation of ADH secretion does not include a ‘feed-back’ mechanism involving a direct action of circulating ADH on the hypothalamic-neurohypophyseal system.