1. The effects of indomethacin on water excretion during both vasopressin stimulation and inhibition were studied in control subjects and in patients with sickle cell anaemia. 2. In the control group as well as in the group of patients with sickle cell anaemia sodium and urea retention occurred after indomethacin in the water-depleted state. During water loading, indomethacin induced sodium retention without urea reabsorption. 3. In healthy volunteers indomethacin increased urinary osmolality during water deprivation, but not after water loading. In contrast, in patients with sickle cell anaemia indomethacin caused a rise in urinary osmolality during water loading, but not after deprivation. 4. The findings support the view that indomethacin promotes solute reabsorption in the distal tubule. 5. From our observations we conclude that renal prostaglandins are not involved in the urinary concentrating defect of patients with sickle cell anaemia. On the other hand, the normal diluting capacity in sickle cell anaemia appears to depend on renal prostaglandins.