The relationship of age to the circadian rhythms of melatonin and cortisol was investigated in 44 men and 27 women (age range 19-89 years). Subjects were physically and psychiatrically normal. Four hourly serial blood samples were drawn from 8:00 AM until 8:00 AM the next day, with additional samples at 10:00 PM and 2:00 AM. The indoor illumination was restricted to 300 lux during day and 50 lux during the night. Plasma melatonin and cortisol were estimated by radioimmunoassay. Results show that the means of melatonin and cortisol values decreased significantly with age when the subjects were divided into three age groups, i.e., 19-25 years, 42-65 years, and 66-89 years. They also showed a significant negative correlation with age. The acrophases of the two hormonal rhythms, however, showed different relationships to age. The acrophase of melatonin rhythm showed a positive correlation with age (r = 0.38, p less than 0.001), and cortisol showed a negative correlation with age (r = -0.56, p greater than 0.001). It is suggested that this may indicate a weakened responsiveness of the circadian system in the elderly to the day-night cycle and an altered relationship between the pacemakers driving melatonin and cortisol circadian rhythms. This may thus represent a biomarker for the intrinsic process of the aging of the brain.