1. The mechanism of the diuretic effect of the kappa opioid receptor agonist spiradoline was investigated in 10 healthy male subjects in a placebo-controlled, double-blind cross-over study. 2. Urine volume and osmolality, plasma vasopressin and Doppler renal blood velocity indices were recorded for 1.25 h before and 6 h following injection. 3. Spiradoline caused a significant increase in urine output which was antagonized by high but not low dose naloxone. The urine increase was accompanied by a significant decrease in osmolality which was also antagonised by high but not low dose naloxone. 4. Spiradoline had no effect on plasma vasopressin concentration or on renal blood velocity indices. 5. We conclude that kappa agonists induce diuresis in humans by a mechanism not involving suppression of vasopressin or changes in renal blood velocity indices.