We investigated the effects of two low doses of interferon-α (IFN-α) on nocturnal sleep in 18 healthy men by means of polysomnographic sleep recordings. At 1900 h, human recombinant IFN-α (1000 or 10,000 U/kg body weight) or placebo was administered subcutaneously. Between 2300 h and 0700 h subjects were allowed to sleep. In general effects were stronger at the dose of 10,000 than 100 U/kg body weight of IFN-α. Although, after IFN-α subjects experienced increased fatigue, the cytokine impaired the quality of nocturnal sleep. The higher dose of IFN-α suppressed slow wave sleep (17.8 ± 2.0% vs 25.2 ± 2.6% following placebo, P < 0.003) but increased time spent in shallow sleep (P < 0.05) during the first half of sleep time. Rapid eye movement (REM) sleep latency was postponed (P < 0.02) and time spent in REM sleep was significantly decreased after IFN-α (P < 0.04). The impairing influence of IFN-α on sleep in humans is in contrast with findings of sleep promoting effects of this cytokine in animals. Our data suggest that endogenous IFN-α may be a factor responsible for alterations of sleep, e.g. in the course of viral infections. (C) 2000 Academic Press.