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BACKGROUND: Patients with cancer often suffer from fatigue and decreased quality of life which might be related to the breakdown of essential amino acid tryptophan. METHODS: In 50 patients with lung cancer we examined fatigue and the deterioration of quality of life in patients using the Functional Assessment of Cancer Therapy Anemia (FACT-An) and -Fatigue (FACT-F) subscales of FACT-General and the Mental adjustment to Cancer (MAC) questionnaires. Results were compared with tryptophan breakdown as well as serum concentrations of immune activation markers. RESULTS: Scores of psychological tests correlated significantly with tryptophan breakdown and with circulatory markers of inflammation. However, immune activation and tryptophan breakdown were not related to MAC scores. CONCLUSIONS: Tryptophan breakdown relates with fatigue and impaired quality of life in patients with lung cancer, while declining tryptophan levels are not associated with patients'coping strategies.