By using the Sperber technique in nonanesthetized chickens, it was found that amiloride was actively secreted by the renal tubule. This active secretion could be blocked by the simultaneous infusions of the organic cations guanidine, quinine and mepiperphenidol, but not by the organic anion probenecid. This suggested that amiloride was transported by the organic cation transport system of the renal tubule. A significant part of the amiloride which bypassed the infused kidney was taken up by the peripheral tissues, resulting in a recovery of amiloride smaller than that of simultaneously infused p-aminohippurate. During the infusion of amiloride, a dose-dependent ipsilateral mild natriuresis was observed. A maximum ipsilateral antikaliuretic effect and increase in pH were found when 5 X 10(-9) mol/kg.min of amiloride were reaching the infused kidney. It is concluded that amiloride is secreted from blood to urine by the proximal tubule and exerts it natriuretic and kaliuretic effects at the luminal surface of the distal tubule.