Hydrocortisone has long been the treatment of choice for congenital adrenal hyperplasia (CAH). However, treatment with this medication remains problematic. Patients with 21-hydroxylase deficiency CAH have significant diurnal variation in the secretion of 17-hydroxyprogesterone (17OHP). When considering treatment strategies, this variation must be considered along with the pharmacokinetic and pharmacodynamic properties of exogenous glucocorticoids. Orally administered hydrocortisone is highly bioavailable, but it has a short time to maximum concentration (T(max)) and half life (T(1/2)). While prednisone has a somewhat longer T(max) and T(1/2), they remain relatively short. There have been several studies of the pharmacodynamics of hydrocortisone. We present data indicating that the maximum effect of hydrocortisone in CAH patients is seen 3 hours after a morning dose. After an evening dose, suppression of adrenal hormones continues until approximately 0500 the next day. In both situations, however, there is a large degree of intersubject variability. These data are consistent with earlier published studies. Use of alternate specimen types, possibly in conjunction with delayed release hydrocortisone preparations under development, may allow the practitioner to design a medication regimen that provides improved control of androgen secretion. Whatever dosing strategy is used, clinical judgment is required to ensure the best outcome.