Plasma melatonin concentrations were determined over a period of 24 hours in 20 women with clinical stage I or II breast cancer. In ten of the patients, whose tumors were estrogen receptor positive, the nocturnal increase in plasma melatonin was much lower than that observed in eight control subjects. Women with the lowest peak concentration of melatonin had tumors with the highest concentrations of estrogen receptors. A significant correlation was found between the peak plasma melatonin concentration and the tumor estrogen receptor concentration in 19 of the patients. These data suggest that low nocturnal melatonin concentrations may indicate the presence of estrogen receptor positive breast cancer and could conceivably have etiologic significance.