The properties of the aldosterone antagonists spironolactone and potassium canrenoate in tablet formulations were examined in two studies in healthy subjects, the first study comparing levels of their common major metabolite, canrenone, in plasma and the second study comparing the pharmacological activity of the two drugs in reversing the renal effects of the synthetic mineralocorticoid fludrocortisone. At equal dosage by weight potassium canrenoate yielded peak levels and areas under the curve for canrenone in plasma which were significantly lower than those for spironolactone, and the peak level of canrenone was reached significantly later. Comparison with published work suggests that the experimental formulation of potassium canrenoate had low bioavailability. Spironolactone produced statistically valid log dose-response curves against fludrocortisone as regards sodium excretion, potassium retention and increased urine sodium to potassium ratio. There was no significant log dose-reponse after potassium canrenoate, and a statistically valid estimate of relative potency could not be obtained. The results of the two studies seem inconsistent with the view that canrenone alone is responsible for the pharmacological activity of both drugs, and suggest that a significant part of the activity of spironolactone may be attributable to metabolites other than canrenone.