A possible link between the neurotransmitter, 5-hydroxytryptamine (5-HT), plasma tryptophan, and branched chain amino acids concentration and exercise-induced fatigue is described by the central fatigue hypothesis. 5-HT receptors and neuroendocrine "challenge" tests, using prolactin release as an indirect measure of 5-HT activity were studied by recent investigations. In the present study, the original hypothesis about the role of amino acids in increasing brain 5-HT with a neuroendocrine challenge test on elite athletes diagnosed with unexplained, underperformance syndrome (UUPS) was combined. There was an apparent increased sensitivity of 5-HT receptors in athletes with UUPS compared with fit, well-trained controls, as measured via increased prolactin release following a bolus dose of m-chlorophenylpiperazine , a 5-HT agonist. No changes were observed in plasma amino acid concentrations in either group. There is evidence that well-trained athletes have a reduced sensitivity of 5-HT receptors. The present study suggests that this adaptation may be lost in athletes with UUPS: this might explain some of their observed symptoms.