Replacement therapy for six weeks with human growth hormone (hGH) in deficient children has been shown to produce a significant lengthening of amobarbital t1/2. Studies to define the time course of this effect were carried out and indicate either no change or a minimal change after one to eight days of treatment. The increased t1/2 noted at six weeks persists for at least one year. In contrast to amobarbital, theophylline was found to exhibit a shortening of t1/2 from a mean of 7.52 +/- 4.44 (SD) to a mean of 3.38 +/- 1.23 hours in four subjects. Thus, replacement therapy with hGH results in quantitatively large but opposite changes in the elimination of these two drugs. For both substrates, however, t1/2 after hGH replacement more closely resembles values reported for normal subjects. This suggests that hGH may be a major determinant of in vivo drug elimination.