The objective of this study was to determine the normal range of nocturnal urinary excretion of the major melatonin metabolite, 6-sulfatoxymelatonin (6SMT) in a large sample of healthy fullterm infants (8 and 16 wk old) and assess whether the endogenous production of melatonin changes with season. 6SMT was assessed in urine samples extracted from disposable diapers removed from full-term, 8-(n ϭ 317) and 16-wk-old (n ϭ 93) infants over the nocturnal period (19:00 -08:00 h). In addition, 6SMT was assessed in 8-wk-old (n ϭ 35) healthy infants over the entire 24-h period. 6SMT was determined by an ELISA assay. 6SMT excretion at 8 wk of age exhibited diurnal variations with (mean Ϯ SD) 61 Ϯ 18% of the daily production excreted during the nocturnal period regardless of season. The nocturnal 6SMT values in the entire cohort (at 8 as well as 16 wk of age) were found to significantly depart from normal distribution (Kolmogorov-Smirnov test). A normal distribution was obtained using a natural base logarithmic (ln) transformation of the data. The normal range (2.5-97.5 percentile of the ln 6SMT excretion per night) was thus defined as 4.66 -8.64 (106 -5646 ng/night) for 8-wk-old and 5.19 -9.67 (180 -15,820 ng/night) for 16-wk-old infants. A significant effect of the month of birth on 6SMT production at the age of 8 wk was found (ANOVA, p Ͻ 0.002) with maximal levels produced by infants born in June (summer solstice) and minimal excretion in infants born in December (winter solstice). Short-photoperiod-born infants excreted on average about threefold less 6SMT compared with long-photoperiod-born infants (t test, p ϭ 0.01). The seasonal variations were no longer present at 16 wk of age. No effect of breast-feeding at the time of sampling on seasonality of 6SMT was found. Normal ranges for the nocturnal urinary excretion of 6SMT in full-term infants at 8 and 16 wk of age are defined. This enables the evaluation of nocturnal 6SMT excretion as a prognostic and diagnostic factor for child development. The strong effect of season on the normal excretion of nocturnal 6SMT at 8 but not 16 wk of age suggests prenatal influence of the photoperiod on the ontogeny of melatonin. The changes in photoperiod are major environmental cues for initiating seasonal acclimatization of thermoregulatory mechanisms and reproduction. In all mammals studied to date, including humans, the nocturnal production of melatonin by the pineal gland reflects the photoperiod (1, 2) and plays a key role in seasonal acclimation. Humans are not considered photoperiod sensitive, although some disorders such as seasonal affective disorders (3) and cluster headache (4) have been associated with a particular season.Sudden infant death syndrome (SIDS) was shown to occur more frequently during the winter months, during the night, and during the first months of life (5). Some evidence links pineal dysfunction and impaired development with increased prevalence of SIDS (6, 7). A delayed melatonin production was found in infants who had experienced an apparent lifethreate...