Substantial amounts of tetrahydrobiopterin and 6-methyltetrahydropterin can be detected in CSF when these pterins are given peripherally to patients with hyperphenylalaninemia due to defective biopterin synthesis. Our results suggest that administration of either of these pterins in proper doses may prove to be a treatment not only for the impaired peripheral phenylalanine metabolism, but also for the neurological disorders that are characteristic of the varient forms of hyperphenylalaninemia due to defective BH4 synthesis or metabolism. With respect to more general applications, administration of large doses of tetrahydropterins could provide a novel way to increase the biosynthesis of catecholamines and serotonin in both the brain and periphery, and could therefore be useful in the treatment of other human disorders suspected to result from deficits in biogenic amine biosynthesis, such as in Parkinson's disease and certain forms of depression.