HPA is either due to phenylalanine hydroxylase deficiency or to BH4 deficiency. The latter should be excluded in all newborns with HPA using three methods: (1) oral BH4 loading test; (2) measurement of dihydropteridine reductase (DHPR) activity in erythrocytes; (3) investigation of the urinary pterin pattern. From 1979 until 1987 seven patients with BH4 deficiency have been detected in Munich. One of two girls with severe 6-pyruvoyl tetrahydropterin synthase (PTS) deficiency has been treated since the age of 7 weeks. Her psychomotor development is now, at the age of 11 years, normal whereas the other girl, 13 years of age, who has been treated since the age of 7 years, shows marked developmental delay. Three out of four patients with partial PTS deficiency (now 6-9 years of age) developed normally, the 4th patient (6 years old), however, presents with slight psychomotor disabilities. Early treatment of a patient with DHPR deficiency was highly unsatisfactory. This boy died at the age of 23 months.