Nocturnal cytokine levels were measured serially in 12 healthy male volunteers for 12 h, including 8 h of polygraphically monitored nocturnal sleep. Plasma concentrations of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were determined in 30-min intervals by enzyme-linked immunoadsorbent assays. In some subjects cytokines were not detectable at all. In the remaining volunteers (27% for IL-1 beta, 58% for IL-6 and TNF-alpha, respectively) occasional values near to the detection limits (DL) of the assays could be measured. With respect to IL-1 beta and IL-6, plasma levels above the DL were significantly more frequent during sleep than during the preceding time of wakefulness. No temporal association with NREM or REM episodes could be shown. TNF-alpha values above the DL were randomly distributed across the 12-h period investigated. It is concluded that in a considerable percentage of healthy subjects small amounts of cytokines are released at night. Release of IL-1 beta and IL-6 is temporally associated with sleep, whereas the release of TNF-alpha is not. It remains to be established whether nocturnal cytokine release reflects either an interaction between sleep and host defense mechanisms or a sleep-independent circadian rhythmicity.