The pineal gland produces many neurohormones that affect the function of the brain. One of these hormones, melatonin among other functions, shows oncostatic properties against some malignant tumors. Our investigations confirmed the oncostatic effect of this compound based on (a) the measurements of melatonin in the serum of melanoma patients, (b) 5-hydroxyindole-O-methyltransferase activity in the pineal of patients with malignant tumors, and (c) the detection of neuromelanin pigment in pineal bodies related to malignancy. Using a radioimmunoassay we have found that blood melatonin content is 4-5-fold increased in patients with the active phase of malignant melanoma. In healthy control subjects of both sexes (n = 6) between the ages 30-35 years at 10:00 a.m. serum melatonin varies between 0.47-0.65 nmol/l serum or 1.44-2.14 pg/mg serum protein. In contrast, in melanoma patients (n = 16) serum melatonin ranges from 2.07 to 6.20 nmol/l serum or 9.70-20.86 pg/mg serum protein. In another study in normal subjects (n = 24) serum melatonin level shows variations between 0.40 and 0.57 nmol/l serum or 1.75 and 2.32 pg/mg serum protein. Melanoma patients (n = 100) generally had an increased serum melatonin level ranging between 1.55 and 2.18 nmol/l serum or between 9.37 and 14.86 pg/mg serum protein. Twenty-four melanoma patients were tested several times during the duration of the disease and showed that surgical removal of the tumor resulted in a reduction of the serum melatonin level in 5 cases, remission was associated with an increase in 17 cases and in 2 cases treatment caused no change. Measurement of 5-hydroxyindole-O-methyltransferase activity in post mortem pineal glands revealed that it was significantly greater in cancer patients (n = 110) as compared to other diseases (n = 30); carcinoma of the esophagus, 12.75 +/- 2.38 nmol/h/mg protein; stomach, 9.74 +/- 1.62; colon, 14.84 +/- 3.97; lung, 9.28 +/- 1.58; kidney, 7.35 +/- 0.96; prostate, 6.02 +/- 0.93; soft palate, 0.62 +/- 0.18; leukemias, 10.96 +/- 2.80; lymphomas, 10.96 +/- 2.80; glioblastoma multiforme, 11.87 +/- 3.15; multiple myeloma, 1.46 +/- 0.42 and cardiovascular disease, 0.95 +/- 0.21. Post mortem histological examinations of isolated pineal bodies have shown that several glands contained a pigment, neuromelanin. A comprehensive study on pineals from a variety of diseases (n = 120) revealed that the pineal pigment content showed an inverse relation with the prevalence of malignancy.