Phenylketonuria (PKU) is a genetic disorder characterized by hyperphenylalaninemia. Treatment involves dietary phenylalanine restriction to prevent mental retardation. Because phenylalanine is involved in tyrosine synthesis and tyrosine is a catecholamine precursor, low tyrosine may lead to brain dopamine deficiencies. Because dopamine is involved in the modulation of prefrontally orchestrated executive functions, deficiencies may lead to executive impairments. Despite treatment, impairments in executive cognitive functions have been reported in young children with PKU. Outcome beyond middle childhood has not been extensively investigated. In this study, PKU-affected adolescents (N= 18) with normal-range IQ scores completed neuropsychological tests, and their performance was compared with unaffected peers (N= 16) and chronically ill controls (N= 17). Results demonstrated that the overall performance of the PKU group did not differ from that of the other two groups, but that performance of the PKU proband was associated with phenylalanine and tyrosine levels, and most strongly with phenylalanine-to-tyrosine ratios at several points in development. These findings provide a preliminary test of the dopamine hypothesis of PKU as it applies to adolescents and young adults.