Nine healthy volunteers received a single oral dose of 200 mg spironolactone, once during fasting conditions and once immediately after a standardized breakfast. Serum concentrations of spironolactone and its metabolites 7 alpha-thiomethylspirolactone, 6 beta-hydroxy-7 alpha-thiomethylspirolactone, and canrenone were determined by HPLC for 24 hours after dosing. By taking spironolactone with food, the mean (+/- SD) AUC (0 to 24 hours) of the parent drug increased from 288 +/- 138 (empty stomach) to 493 +/- 105 ng X ml-1 X hr (P less than 0.001). The AUC (0 to 24 hours) of the three metabolites together also increased significantly from 8511 +/- 2062 (empty stomach) to 11219 +/- 2471 ng X ml-1 X hr (P less than 0.01). The mean (+/- SD) percent increase in AUC (0 to 24 hours) of spironolactone when it was given with food, compared with the ingestion on an empty stomach (95.4% +/- 66.9%), was much more pronounced than the corresponding increase of 7 alpha-thiomethylspirolactone (45.4% +/- 33.7%), 6 beta-hydroxy-7 alpha-thiomethylspiro-lactone (21.8% +/- 21.5%), and canrenone (40.7% +/- 26.3%). These observations indicate that food promotes the absorption of spironolactone and possibly decreases its first-pass metabolism.