Objective.-To investigate headache-related serum melatonin levels and melatonin excretion rhythmicity in patients with hypnic headache (HH). Background.-Strict sleep dependency of headache attacks is a pathognomonic feature of HH. Changes in melatonin levels, a marker for circadian rhythm, are assumed to play a pivotal role in the pathophysiology of HH. Methods.-Serum melatonin levels were acquired in nine patients with HH and nine age-and gender-matched healthy controls over a 20-hour time period (12 pm, 4 pm, 7 pm, 10 pm, time of headache, and 8 am). Results.-No significant changes of melatonin levels could be detected comparing HH patients and healthy controls. Melatonin excretion rhythmicity was not significantly altered in patients with HH (Mean melatonin level in ng/mL +/- SD, patients vs controls at 12 pm: 21.5 +/- 9.5 vs 13.6 +/- 6.3 [P = .077], 4 pm: 18.4 +/- 8.4 vs 14.0 +/- 4.7 [P = .222], 7 pm: 19.4 +/- 5.1 vs 15.1 +/- 4.5 [P = .094], 10 pm: 59.5 +/- 45.0 vs 29.4 +/- 12.7 [P =.136], headache time: 96.9 +/- 68.3 vs 49.1 +/- 22.8 [P = .94], and 8 am: 31.6 +/- 18.3 vs 26.7 +/- 15.6 [P = .489]). Conclusion.-This study is not able to confirm a significant role of melatonin concentration changes in the pathophysiology of HH and vetoes that melatonin deficiency plays a major role in the pathophysiology of the disorder.