A first study of DSIP (= synthetic delta sleep-inducing peptide) application to humans was carried out in six normal volunteers (four males and two females) under extensive psychophysiologic observations and measurements in a double-blind cross-over design. DSIP was applied as slow intravenous infusions at a dosage of 25 nmol/kg in the morning. The subjects immediately reported a feeling of sleep pressure, and sleep increased by 59% (median of total sleep time) within a 130-min interval after the treatment as compared with placebo. Delayed effects on subsequent night sleep were shorter sleep onset, reduced percentage of stage 1, and better sleep efficiency. Nevertheless, sophisticated behavioral and EEG analyses revealed no sedation in the classic pharmacologic way. The results suggest that DSIP in humans is also efficacious by sustaining natural sleep functions. The compound was well-tolerated and no psychologic, physiologic, or biochemical side effects were observed.