Increased levels of octopamine in adrenergic nerve terminals and plasma have been implicated in the circulatory and renal disturbances of chronic hepatic failure. Little is known about its renal actions in normal animals. In the present study, DL-octopamine was administered both i.v. and into one renal artery of anaesthetized dogs in doses ranging between 25-200 micrograms/min (1.6-20 micrograms/kg/min). Octopamine was hypertensive in doses of 100 micrograms/min and more and this change was associated with a significant decrement in GFR and renal perfusion. This amine also exerted a direct tubular effect since decreased excretion of sodium and water occurred in the absence of blood pressure or renal perfusional changes when given i.v. When given into one renal artery octopamine produced only an ipsilateral antidiuresis and antinatriuresis, in the absence of any change to GFR or renal perfusion. Lithium clearances suggest that octopamine acts beyond the proximal tubule in altering the tubular reabsorption of salt and water. Because octopamine was found to increase blood pressure in the presence of a hypertensive infusion of noradrenaline, it is likely that this amine exerts a primary pharmacological effect rather than liberating noradrenaline from nerve terminals. Saline expansion (7% body weight), acute biliary obstruction, chronic cirrhosis with ascites, and chronic thoracic caval constriction with the production of ascites all abolish the effect of octopamine when administered at 100 micrograms/min. Though octopamine may directly influence renal perfusion, its possible role in liver disease remains uncertain.