The potency of single doses of a new aldosterone antagonist, prorenoate, in reversing the renal effects of the synthetic mineralocorticoid fludrocortisone was compared to that of spironolactone in a double‐blind balanced crossover study in 12 healthy subjects, The potency of prorenoate potassium as related to elevation of the urinary log 10 10 Na/K ratio (2.69:1) and as related to potassium retention (3.75:1 ) was significantly higher than that of spironolactone. Prorenoate produced greater natriuresis (1.64: 1) but the difference was not significant. There was evidence for a qualitative difference between spironolactone and prorenoate; the latter significantly more potent in retaining potassium than in increasing sodium excretion. The simple methodology described is based on standard bioassay principles, Yielded a valid and sensitive comparison of the two drugs, and should prove useful in the evaluation of other aldosterone antagonists.