Glucose intolerance, reduced sleep efficiency, and disturbed circadian rhythmicity occur in aging. In normal young subjects, glucose regulation is modulated by sleep and circadian rhythmicity. To examine age-related alterations in the temporal pattern of glucose tolerance and insulin secretion, eight modestly overweight healthy older men, eight weight-matched young men, and six young lean men were studied during constant glucose infusion for 53 h. Levels of glucose, insulin, C-peptide, and growth hormone (GH) were measured every 20 min. Rates of insulin and GH secretion were calculated by deconvolution. In older volunteers, sleep ws shallow and more fragmented than in young subjects but was nevertheless associated with robust glucose elevations. However, postsleep increases of insulin secretion were markedly dampened. During wakefulness, the normal morning-to-evening increase in glucose was preserved in the elderly, but insulin secretion failed to increase proportionately. Thus decreased glucose tolerance in aging is associated with insulin resistance and also with a relative insensitivity of the beta-cell to the modulation of glucose regulation by sleep and circadian rhythmicity.