Spironolactone treatment was associated with a decrease in the plasma antipyrine half-life in all 9 volunteers studied. This was associated with an increased excretion of 4-OH antipyrine but not 3-hydroxymethyl antipyrine in their urine. The plasma antipyrine disappearance rate correlated with the excretion rate of 4-OH antipyrine in the urine. Spironolactone increased the excretion of 6-βOH cortisol in the urine. These data provided indirect evidence that spironolactone is an inducer of hepatic drug hydroxylation in man.