We studied 13 children with 21-hydroxyalse deficiency to explore the immediate potential suppressive effect of hydrocortisone dose schedule on the adrenal cortex. They were given 20 mg/m2 daily in a controlled trial. After random administration of a greater dose in the morning (7 patients) or at night (6 patients), we measured plasma levels of 17-hydroxyprogesterone, testosterone, and androstenedione at times-24, 0, 2, 4, and 6h. Considerable fluctuation of the steroid levels, unrelated to the drug intake, was observed. There was no statistically significant differences between the "morning dose" and "night dose" groups for any steroid. We conclude that; (i) the greater night dose did not avoid the 17-hydroxyprogesterone morning peaks, and (ii) the variation in plasma steroid levels is so marked that a single morning sample is unreliable to reflect the degree of adrenal suppression.