The primary factor determining plasma melatonin levels is the prevailing light–dark environment.8 The rhythmic production and secretion of melatonin is synchronized by the light–dark cycle. Typically, daytime is associated with low plasma melatonin levels and nighttime is associated with high levels (see Fig. 10-3).6 Blind humans with no retinal light perception exhibit free-running melatonin cycles, with periods of ˜24.7 hours. In these persons, the highest plasma melatonin values can occur either at night or during the day.9