The influence of 600 mg acetylsalicylic acid (ASA) on the renal excretion and clearance of canrenone, the principal unconjugated metabolite of spironolactone, was examined in a double-blind crossover study in six healthy subjects. ASA significantly reduced the urinary excretion, and the fractional excretion, of canrenone between 4 — 6 hours after administration of 50 mg spironolactone. The pharmacological activity of spironolactone, assessed simultaneously by alterations in fludrocortisone-induced urinary electrolyte changes, was slightly but not significantly reduced. The reductions in urinary canrenone excretion correlated with changes in the urinary log 10 Na/K ratio. The results suggest that canrenone may be actively secreted at the proximal renal tubule, and that secretion is blocked by ASA or its conjugates. This is a possible mechanism for the pharmacological interaction between ASA and spironolactone which has been described previously.