A 10-h nocturnal intracerebroventricular infusion of 2 or 3 sleep substances such as 2.5 nmol delta-sleep-inducing peptide (DSIP), 2.0 nmol muramyl dipeptide (MDP) and 10 pmol uridine resulted in a significant, combination-dependent change in sleep-waking dynamics, which was quite different from the time-course sleep promotion induced by the single administration of each substance. The DSIP-MDP combination was characterized by a profound increase in SWS only at the middle infusion period. PS was little affected. The DSIP-uridine combination exerted a slight increase in SWS at the late infusion period with little change in PS parameters. The MDP-uridine combination caused a marked increase in both SWS and PS only at the early to middle infusion period. The DSIP-MDP-uridine combination induced an extremely large increase in SWS at the early to middle phase of the infusion period. PS significantly increased only at the early phase. These results may suggest that the sleep substances acted in tandem, either synergistically or antagonistically, on the sleep regulatory mechanism.