A female born near term weighing 2.7kg had blood phenylalanine level of 4-6mg/dl at the age of 3 days. Subsequently, blood phenylalanine level was >20mg/dl and 58.4mg/dl with blood tyro-sine 0.65mg/dl in the 3rd and 4th weeks of life. In the first week of life, the baby developed feeding problems, poor suck and poor muscle tone. Urinary neurotransmitters metabolites (VMA, HVA and 5HIAA) were found to be normal. The diagnosis of classical PKU was made and low phenylalanine diet was started. At the age of 6 months, in spite of good control of blood phenylalanine levels, the baby was found to be delayed, hypotonic, failed to gain weight and functioned at 2-3 months. She was also noted to be tremulous and had choreoform movement. An EEG and CT scan of the head were normal. Urinary pterins showed a profound deficiency of neopterin (N) and biopterin (B) (N=88.5ng/mg creatininine, B=36.6ng/mg creatinine; values which are 1% of the normal levels). However, the ratio of N/B was normal. The same deficiency was found in the plasma and CSF. The patient was placed on L-DOPA, Carbidopa and 5-hydroxytryptophan which caused clinical improvement. Since defects in the synthesis of biopterin cause very high levels of neopterin, the deficiency of neopterin in this child is the result of GTP-cyclohydrolase deficiency, a step required for the formation of dihydroneopterin triphosphate; similar to the case of Niederwieser et al (Eur J Peds 138:97, 1982). Normal N/B ratio is not sufficient to rule out defects in the synthesis of tetrahydrobiopterin.