: OBJECTIVES: The synthesis of melatonin, an endogenous compound synthesized by the pineal gland in the brain, is reported to be depressed in patients with primary cancers of the breast, prostate, stomach and rectum. It is not known whether patients with brain cancer exhibit altered melatonin synthesis. Also unknown is whether radiotherapy given to the region of the brain where the pineal gland is located affects the synthesis of melatonin. This information could be relevant to the clinician for the successful treatment of brain cancer patients since melatonin has been reported to be a potent oncostatic agent. METHODS: Urinary levels of 6-sulphatoxymelatonin, the chief metabolite of melatonin, are routinely used as an index of pineal melatonin production and secretion. In this study, the concentrations of 6-sulphatoxymelatonin (aMT6S) excreted in the urine before and during radiotherapy of patients with primary or metastatic brain cancer were determined and compared with the values obtained in breast or lung cancer patients who also received radiotherapy (excluding exposure of the brain where the pineal gland is located). RESULTS: The results showed a wide variation in the mean concentration of aMT6S excreted in the urine. CONCLUSION: The data from this preliminary study suggested that radiotherapy given to the region of human brain, where the pineal gland is located, does not significantly affect the excretion of aMT6S, the chief metabolite of melatonin.