Identical pharmacological amounts of synthetic adrenal steroids were given on alternate days and at eight-hour intervals to nine adult subjects. The effects of the two administration regimens on serum and urine sodium, potassium, calcium, glucose, and urine nitrogen levels, and creatinine clearance were monitored. During short-interval steroid administration daily urine nitrogen, potassium, calcium, and glucose levels were significantly increased (P<0.05). Only urine calcium and glucose levels were significantly increased during the alternate-day regimen. Additional studies demonstrated that the effects of the alternate-day dose on fasting serum glucose were dissipated before the next scheduled dose. This was not true with the shorter-interval dose. These data suggest that the undesirable catabolic effects of glucocorticoids do occur with alternate-day administration but may be less severe than when the steroid is given frequently in divided doses.