1. In order to study the effect of overhydration on body potassium, experiments were performed on pair-fed rabbits, one of which was maintained continuously on vasopressin and given extra water (60–90 ml day−1 kg−1) for 6–8 days, while the other served as control.
2. Overhydrated rabbits excreted significantly more potassium (53%) in their urine than control rabbits and accumulated a mean potassium deficit of 65·0 mmol, significantly higher than the mean value of 37·1 mmol in the control rabbits.
3. In the overhydrated rabbits, potassium fell significantly in both erythrocytes, from 266 to 173 mmol/kg of dry cells, and also in muscle, from 435 to 341 mmol/kg of fat-free dry solids. Neither changed significantly in the control animals.
4. Overhydration in the presence of vasopressin leads to potassium depletion in the rabbit and a similar phenomenon might be expected in man. Potassium depletion due to overhydration might account for the hypokalaemia and reduction in exchangeable potassium observed in some patients with the syndrome of inappropriate secretion of antidiuretic hormone.