This study describes absorption, excretion, and metabolism of [20−3 H]-spironolactone (SP) in 5 healthy men. After a single oral dose (200 mg + 200 p,Ci) of the drug given in alcoholic solution, the peak serum levels of the ethyl acetate-extractable tritium and the dethioacetylated metabolite canrenone were 763 ± 400 ng/ml (mean ± SD) and 415 ± 145 ng/ml, respectively. These levels occurred within 3 hr. The serum half-life (T½) of the extractable materials was 37.3 ± 6.53 hr. Canrenone levels declined in two phases. The Tdrom 2.5 to 12 hr was 4.42 ± 1.07 hrandfrom 12 to 72 hr was 16.8 ± 2.75 hr. In the blood both SP and canrenone were confined largely in the plasma, and their protein binding exceeded 89% at concentrations of 550 and 710 ng/ml, respectively. In 5 days 31.6 ± 5.87% of the radioactivity was excreted in the urine and 22.7 ± 14.1% in the feces. Unchanged SP was not detected in the urine. The major urinary metabolites were canrenone (5.04 ± 2.83% of dose), 6ß-OH-sulfoxide (5.21 ± 0.93% of dose), and canrenoate ester glucuronide (6.2% of dose).