The available data on potential alterations in serum melatonin (MLT) levels during a human lifetime are fragmentary and inconsistent. We, therefore, measured day- and nighttime serum MLT concentrations in 367 subjects (210 males and 157 females), aged 3 days to 90 yr. Blood samples were collected between 0730 and 1000 h and between 2300 and 0100 h. Serum MLT levels were measured by RIA. The mean nighttime serum MLT concentration was low during the first 6 months of life, i.e. 27.3 +/- 5.4 (+/- SE) pg/mL (0.12 +/- 0.02 nmol/L). It then increased to a peak value at 1-3 yr of age [329.5 +/- 42.0 pg/mL; (1.43 +/- 0.18 nmol/L)], and it was considerably lower [62.5 +/- 9.0 pg/mL; (0.27 +/- 0.04 nmol/L)] in individuals aged 15-20 yr. During the following decades serum MLT declined moderately until old age (70-90 yr of age), i.e. 29.2 +/- 6.1 pg/mL (0.13 +/- 0.03 nmol/L). This biphasic MLT decline follows 2 exponential functions with different slopes (from age 1-20 yr: r = -0.56; P less than 0.001; y = 278.7 X e -0.09x; from age 20-90 yr: r = -0.44; P less than 0.001; y = 84.8 X e -0.017x). The decrease in nocturnal serum MLT in children and adolescents (1-20 yr) correlated with the increase in body weight (r = -0.54; P less than 0.001) and body surface area (r = -0.71; P less than 0.001). At a later age (20-90 yr) there was no correlation among these variables. Daytime serum MLT levels were low and no age-related alterations were found. This study revealed major age-related alterations in nocturnal serum MLT levels. The negative correlation between serum MLT and body weight in childhood and adolescence is evidence that expansion of body size is responsible for the huge MLT decrease during that period. The moderate decline at older ages must derive from other factors.