Following establishment of steady state plasma concentrations of ticrynafen in the mongrel dog, the intravenous injection of large doses of p -aminohippurate (PAH) or sodium salicylate reduced or blocked the urinary excretion of ticrynafen. In a similar manner, the intravenous administration of ticrynafen reduced the urinary excretion of PAH in preloaded dogs. Since PAH and salicylate are actively secreted by a renal tubular organic anion transport system, these data were interpreted as evidence of an active tubular secretion of ticrynafen. The natriuresis and uricosuria which result from the administration of ticrynafen to the mongrel dog were reduced by PAH and salicylate at doses of these compounds which effectively blocked the secretion of ticrynafen. These results demonstrate that in the dog, the natriuretic and uricosuric activity of ticrynafen results from the presence of ticrynafen in the tubular lumen.