Screening of 1,042,000 Greek newborns for PKU using the Guthrie test, revealed a mean incidence 1:10,420 for Hyperphenylalaninaemia (1:24,233 classic PKU and 1:18,280 benign variants). The mean Phe concentration of the first sample (3-15 days) was 14.1 mg/dl (6-40) for PKU while, for variants, it was 7.7 mg/dl (4-16). Using 4 mg/dl as the limit under which no repeat test was requested, no case of PKU has been missed. On the whole, 100 newborns with persistent Hphe have been detected: 43 proved to be classical PKU and 57 benign variants. After excluding BH4 deficiency, Phe blood level has been kept below 10 mg/dl in all Hphe babies during the first 2 years of life, irrespective of the type of Hphe. All treated Hphe babies have developed normally. Discrimination between PKU and variants was achieved in the 6-18 months of life with protein loading tests. Treated PKU children had the lowest Phe concentrations during the first year of life (mean 5.1 mg/dl). From then on, a steady yearly increase was observed. Their mean IQ in the Stanford-Binet L-M dropped from 107.2 in the second year to 95.8 in the sixth year. A high negative correlation is not clearly shown, probably due to the small number of cases. PKU clinic (supportive and counselling group therapy) along with individual consultations have proved to be helpful, as has the promotion of diet compliance. The need to individualize each of Hphe before deciding upon ways of treatment is stressed and a protocol to be followed for each Hphe is proposed.