The apparent age-related decline in melatonin production has been thought to continue in a secular manner across the lifespan. While it is clear that melatonin levels in children and adolescents are elevated compared to older individuals, the question of whether there is a sudden or gradual change has not been adequately addressed. In this study, we report the excretion of the melatonin metabolite, 6-sulfatoxymelatonin in 253 subjects aged between 21 and 82 yr. The correlation with age was significant (r = -0.24; P < 0.05). When the data was analysed by ANOVA using 5-yr age spans, there was a significant effect of age, but post hoc analysis indicated that after 25 yr of age there was no significant decline in excretion of the metabolite. Thus, although the oldest subjects excreted 36% less melatonin metabolite than the youngest, the decrease occurred at a very early age. In the second part of the study, we re-evaluated the data from seven previous studies that measured plasma melatonin levels or metabolite excretion across a wide range of ages and 11 studies comparing young versus older subjects. Statistical analysis by ANOVA again suggested that the changes in melatonin occurring with age were essentially complete before 30 yr of age. The youngest subjects produced at the most twice the amount of melatonin as the oldest subjects. Finally, we evaluated the mean plasma melatonin levels in 144 groups of normal subjects reported in 137 separate publications with respect to age. Again, whereas there was a significant correlation with age, ANOVA showed that there was no difference between groups after 35 yr of age, and the oldest groups had levels that were only 43% of the youngest groups. We conclude that melatonin production is lower in older people, but that the change occurs very early in life, around 20-30 yr of age.