The postnatal developmental profiles of two enzymes that oxidize Γ-hydro-xybutyrate (GHB) were examined during the period when the brain concentration of GHB was changing from the higher fetal level (7 µM) to the lower adult level (2 µM). At 20 days of age, the maximal oxidative capacity (Vmax of GBH dehydrogenase (GHB-D) in the brain reached a rate that was approximately 50% greater than either adult or 18-day fetal values. The Vmax for GBH-oxoacid transhydrogenase (GHB-T) in the brain was negligible at 18 days of gestation but increased 40-fold by 20 days and 100-fold by 70 days after birth. In contrast to the brain, the GHB concentration in the kidney remained at approximately 65% of the adult level from birth to 15 days of age and then rose to adult levels. The activities of both GHB-D and GHB-T were 20% of their adult values in the newborn kidney, and both enzymes increased to near adult activities by 20 days. It appears that GHB-D is the predominant catabolic enzyme for GHB in the fetal and neonatal brain, whereas in the kidney both enzymes participate from the earliest time examined.