In a group of healthy humans, plasma vasopressin (AVP) levels fell on drinking either Tyrode or mannitol solutions isosmotic with plasma. Both the timing and magnitude of the fall were appropriate to account for the transient diuresis which followed the drinking. Although plasma expansion follows drinking Tyrode solution it occurred too late to account for the fall in plasma AVP. It was also too small to inhibit AVP secretion. Even though plasma volume tended to contract on drinking isosmotic mannitol solution a fall in plasma AVP and a diuresis occurred, similar to those found after drinking Tyrode solution. These findings appear to eliminate plasma volume expansion as the stimulus for the fall in plasma AVP and the associated diuresis on drinking isotonic fluids. In a further group of human subjects, bypassing the oropharynx by intragastric infusion resulted in a slower onset of diuresis after a water load. We suggest that receptors, as yet undefined, in the upper gastrointestinal tract contribute to the early stages of a water diuresis and account for the apparently inappropriate transient diuresis which follows the drinking of isotonic fluids.