The hormone melatonin plays a key role in coordinating neuroendocrine signals involved in the control of biological rhythms and also appears to be involved in the regulation of cellular proliferation. In this study on patients with gastrointestinal and lung cancer the nocturnal urinary excretion of 6-sulfatoxymelatonin (aMT6s) reflecting pineal melatonin production as well as immunohistochemically detectable proliferating cell nuclear antigen (PCNA) and melatonin were measured in corresponding tumor specimens (6 colorectal, 8 stomach, and 12 lung cancers). Strong positive correlations were detected between aMT6s and PCNA for the different types of tumors analysed (1 > or = Rs > or = 0.736, P < 0.01-0.0001). These findings provide support to the concept of an involvement of the pineal gland in malignancy and suggest that aMT6s-measurements may be considered as a non-invasive tool to estimate tumor cell proliferation. Negative correlations found between urinary aMT6s and melatonin in tumor cells (-0.735 > or = Rs > or = -0.928, P < 0.01-0.0025) could be interpreted as an effort of the pineal gland to secrete melatonin to compensate for the decrease in the number of melatonin-immunopositive cells within tumor tissue where it may possess important regulatory functions.