This study investigated the impact of sleep deprivation on the human circadian system. Plasma melatonin and cortisol, and leukocyte expression levels of 12 genes were examined over 48 h (sleep vs no sleep nights) in 12 young males (mean ± SD, 23 ± 5 yrs). During one night of total sleep deprivation BMAL1 expression was suppressed, the heat shock gene HSPA1B expression was induced, and the amplitude of the melatonin rhythm increased while other high-amplitude clock gene rhythms (e.g. PER1-3, REV-ERB) remained unaffected.Our data suggest that the core clock mechanism in peripheral oscillators is compromised during acute sleep deprivation.