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Abstract: Objective: Higher blood levels of the essential amino acid phenylalanine (phe) have been documented in patients with HIV-1 infection. They may relate to a diminished conversion of phe to tyrosine (tyr) by the enzyme phenylalanine-hydroxylase (PAH). PAH is rate-limiting in the biosynthesis of dopamine, and impaired PAH activity is reflected by an increased phe to tyr ratio (phe/tyr). Methods: Plasma phe/tyr was measured in 107 patients with HIV-1 infection before and after 12months of effective antiretroviral therapy (ART). Results were compared with CD4+ cell counts, HIV-1 RNA levels and concentrations of immune activation marker neopterin. Results: Before ART, phe/tyr was mean±S.D.: 0.99±0.57μmol/μmol. Phe/tyr correlated significantly with plasma and urine neopterin concentrations (rs =0.434, and rs =0.392; both p <0.001) and less strongly with HIV-RNA levels (rs =0.173) and CD4+ counts (rs =−0.182, both p <0.05). After ART, phe/tyr dropped to 0.72±0.16 (=−27%; U =5.21, p =0.01) which was due to an average decline of −14% of phe concentrations from 73.1±34.0μmol/L at baseline to 62.9±17.8μmol/L after ART (U =2.51, p =0.01) and a concomitant increase of tyr concentrations (+13%, U =2.46, p =0.01). In parallel, significant reductions of plasma and urine neopterin concentrations were observed during ART. Conclusions: Increased phe/tyr is frequent in patients with HIV-1 infection and is related to immune activation. ART was found to decrease phe/tyr and this change could indicate and influence on PAH activity. Future studies might be able to show whether the decline of phe/tyr under ART may concur with the often improved neuropsychiatric status in treated patients. [Copyright &y& Elsevier]