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In visually and neurological ly intact humans, the melatonin rhythm may represent the output of a stable oscillator with a signal entrained to the light-dark cycle and relatively free from acute perturbation by stress or changes in other hormones. However, when both are present, they appear linked in time with a phase separation of 4.4-9.3 h. In relation to the melatonin and cortisol rhythms, the presence of one does not require that of the other. Patients with lesions in the neural pathway, described as controlling the pineal melatonin rhythm in animals, had a suppressed plasma melatonin rhythm similar to the depressed cortisol rhythm seen in other patients with lesions of the pituitary-adrenal axis. The stresses of insulin hypoglycemia, pneumoencephalography, and exercise were not associated with a rise in human plasma melatonin, although cortisol or other hormonal markers of stress did increase. Delea, in Biological Markers in Psychiatry and Neurology, 1982 ABSTRACT