Growth hormone regulates the hepatic mRNA levels of α<sub>1</sub>-antitrypsin and two contrapsin-like mRNAs in the rat. To determine whether growth hormone regulates similar serine protease inhibitors in humans, we measured serum α<sub>1</sub>-antitrypsin, α<sub>1</sub>-antichymotrypsin, and antithrombin III by radioimmunodiffusion in 16 growth hormone deficient children before and after growth hormone therapy. Of the 19 determinations made, 17/19 showed an increase in α<sub>1</sub>-antirypsin after administration of growth hormone, 198.6 ± 39.1 mg/dl before growth hormone and 239.4 ± 44 mg/dl after growth hormone (p = 0.005). Specificity of the response for α<sub>1</sub>-antitrypsin was indicated by the fact that neither α<sub>1</sub>-antichymotrypsin or antithrombin III values changed after growth hormone (p = 0.6 and 0.5, respectively). These data are compatible with the hypothesis that growth hormone regulates serine protease inhibitors in humans and suggests that investigation of other members of the serpin gene family might prove fruitful in defining additional growth hormone target genes.