Although the peripheral administration of DSIP (delta sleep inducing peptide) to intact animals does not consistently induce behavioral sleep, potentiation of the effect by d-amphetamine has been established earlier. This study investigated DSIP effects in rats following pretreatment with alpha MPT and/or 1-tryptophan at various dose levels. A clear potentiation was found. Furthermore, pretreatment with methysergide blocked the emergence of sleep signs in various treated groups. It is proposed that the action of DSIP is best understood in the context of mediation via serotonergic mechanisms.