The effect of a selective kappa opioid agonist, U-62,066E, on urine formation in human volunteers was assessed. Volunteers received single intramuscular injections of either placebo or 2, 3, 4, 5 or 6 micrograms/kg of U-62,066E in a randomized, double-blind study. U-62,066E caused dose-dependent maximal increases in urine volume of 2.6 times control in the first 4 hr after administration. A corresponding decrease in urine osmolality to 20% of base-line values occurred. No changes in total urinary Na, K or Cl excretion were identified. Kappa agonists produce a water-only diuresis at low doses in humans. The mechanism of this effect was not examined in this study but probably relates to alterations in antidiuretic hormone activity.