Plasma levels of hydrocortisone were examined following single 60-mg oral doses to healthy male and female volunteers. The doses were administered following an overnight fast with 20 ml or 250 ml of water, or immediately following a standard breakfast. Plasma hydrocortisone levels in individual subjects were adequately described by a simple one-compartment kinetic model incorporating first-order drug absorption and elimination, and an absorption lag-time. The The absorption of hydrocortisone was delayed following the nonfasting treatment, compared to the fasting treatments. Peak drug levels in plasma were significantly reduced, and the time taken to achieve these levels was significantly increased when the hydrocortisone was ingested after food. In order to optimize the consistency of patient response to oral hydrocortisone therapy, the drug should be administered routinely on a fasted stomach.