Background: Few studies have looked at acceptable serum phenylalanine levels in later life in patients with PKU. We examined the oxidative stress status of adolescents and adults with PKU. Methods: Forty PKU patients aged over fifteen years were enrolled, and were compared with thirty age-matched controls. Oxidative stress markers, anti-oxidant enzyme activities in erythrocytes, blood anti-oxidant levels and nitric oxide production were examined. Results: Plasma thiobarbituric acid reactive species and serum malondialdehyde-modified LDL levels were significantly higher in PKU patients than control subjects, and correlated significantly with serum phenylalanine level. Plasma total anti-oxidant reactivity levels were significantly lower in the patient group, and correlated negatively with phenylalanine level. Erythrocyte superoxide dismutase and catalase activities were higher and correlated significantly with phenylalanine level. Glutathione peroxidase activity was lower and correlated negatively with phenylalanine level. The oxidative stress score calculated from these six parameters was significantly higher in patients with serum phenylalanine of 700-800 micro mol/l. Plasma anti-oxidant substances, beta-carotene, and coenzyme Q10 were lower. Serum nitrite/nitrate levels were higher together with low serum asymmetric dimethylarginine. Conclusions: Oxidative stress status is closely linked with serum phenylalanine levels. Phenylalanine in PKU should be maintained at below 700-800 micro mol/l even in adult patients. Adults with phenylketonuria can develop neuropsychological abnormalities as a result of hyperphenylalaninemia. These symptoms can be detected with computerized neuropsychological tests. Brain hyperphenylalaninemia can in turn be measured with use of magnetic resonance spectroscopy. The aim of the study was to assess the brain phenylalanine concentration in hyperphenylalaninemic adults without neuropsychological deficits. Assessment of sustained attention, working memory and inhibitive control was performed in a group of 30 non-compliant adults with phenylketonuria by means of computerized CANTAB system. Brain/blood phenylalanine ratio was analyzed in patients without neuropsychological abnormalities (brain phenylalanine concentration was measured with use of magnetic resonance spectroscopy). Worsening of neuropsychological efficiency correlated with high levels of plasma phenylalanine. Neuropsychological abnormalities were recorded in 28 patients. In the remaining two patients relatively low brain/blood phenylalanine ratios were observed. This finding supports the hypothesis on the presence of mechanisms limiting brain phenylalanine concentration in selected patients with phenylketonuria, which was postulated by other authors. These potential mechanisms could result in lower brain toxicity of hyperphenylalaninemia. It should be stressed, however, that such situation can probably be expected very rarely. The study was sponsored by government research grant NN402329233. Several studies suggested a compromised BMD in HPA affected patients on diet-therapy. Our aim was to assess bone mineralization and evaluate effects of calcium integration and physical activity in HPA patients.