Since the turn of the century, it has been postulated that humoral factors induce sleep. Many compounds were proposed as sleep-factors, but only two of the sleep-peptides have been purified to homogeneity and characterized, so far. One of them, DSIP, was shown to be a nonapeptide of MW 849 and to induce mainly delta-sleep in rabbits, rats, mice, and humans, whereas in cats, the effect on REM sleep was more pronounced. A U-shaped activity curve was determined for the dose as well as for the time of infusion. DSIP-like material was found by RIA and immunohistochemistry in brain and by RIA in peripheral organs of the rat as well as in plasma of several mammals. In addition to sleep, the peptide also has been observed to affect electrophysiological activity, neurotransmitter levels in the brain, circadian and locomotor patterns, hormonal levels, psychological performance, and the activity of neuropharmacological drugs including their withdrawal.