This study tests the hypothesis that elevated postoperative excretion of cortisol is associated with suppression of the nocturnal excretion of 6-sulfatoxymelatonin, the chief metabolite of the circadian hormone, melatonin. Postoperative patients demonstrate circadian rhythm disturbances and suppression of nocturnal melatonin plasma concentration. Since the nocturnal surge in melatonin concentration in normal volunteers is time-locked to the circadian nadir of cortisol concentration, perhaps the attenuation of the nocturnal melatonin surge in postoperative patients results from prolonged elevation in the plasma cortisol concentration. In this observational study performed in 21 patients having unilateral hip or knee arthroplasty, urine was collected every 4 h for the first 48 h after surgery for measurement of urinary 6-sulfatoxymelatonin (EIA) and free cortisol (RIA) excretion. The total (P < 0.05) and peak (P < 0.02) nocturnal 6-sulfatoxymelatonin excretions were lower on the first than the second postoperative night. The nocturnal cortisol nadir preceded the 6-sulfatoxymelatonin surge in 20% of the subjects on night 1 and in 75% of the subjects on night 2. The lack of a consistent relationship between the magnitude or timing of cortisol excretion and 6-sulfatoxymelatonin excretion suggests that cortisol does not mediate postoperative 6-sulfatoxymelatonin suppression.