To examine a possible relationship between pineal function and the sudden infant death syndrome (SIDS), samples of whole blood, ventricular cerebrospinal fluid (CSF) and/or vitreous humor (VH) were obtained at autopsy from 68 infants (45 male, 23 female) whose deaths were attributed to either SIDS (n = 32, 0.5-5.0 months of age; mean +/- S.E.M., 2.6 +/- 0.2 months) or other causes (non-SIDS, n = 36, 0.3-8.0 months of age 4.3 +/- 0.3 months). The melatonin concentrations were measured by radioimmunoassay. A significant correlation was observed for melatonin levels in different body fluids from the same individual. After adjusting for age differences, CSF melatonin levels were significantly lower among the SIDS infants (91 +/- 29 pmol/l; n = 32) than among those dying of other causes (180 +/- 27; n = 35, P less than 0.05). A similar, but non-significant trend was also noted in blood (97 +/- 23, n = 30 vs. 144 +/- 22 pmol/l, n = 33) and vitreous humor (68 +/- 21, n = 10 vs. 81 +/- 17 pmol/l, n = 15). These differences do not appear to be explainable in terms of the interval between death and autopsy, gender, premortem infection or therapeutic measures instituted prior to death. Diminished melatonin production may be characteristic of SIDS and could represent an impairment in the maturation of physiologic circadian organization.