The H1-receptor agonist 2-thiazolylethylamine (2-TEA) given by i.c.v. route dose-dependently increased wakefulness (W) and decreased NREM sleep (NREMS) and REM sleep (REMS) in rats prepared for chronic sleep recordings. The H1-receptor antagonists pyrilamine and diphenhydramine given by i.p. route decreased W and increased NREMS. Pyrilamine prevented the increase of W and decrease of NREMS produced by 2-TEA. However, REMS reduction was not antagonized, what tends to suggest that two different mechanisms could be involved in the 2-TEA-induced effects on NREMS and REMS. Cimetidine which blocks H2-receptors, when given by i.p. route showed no significant effects on sleep and W. Administration of the H2-receptor agonist dimaprit and the H2-receptor antagonists cimetidine, metiamide and ranitidine by i.c.v. route induced the appearance of high voltage spikes at cortical leads, thus leaving inconclusive the matter of their effects on sleep and wakefulness. Our results tend to support the proposal that the H1-receptor intervenes in sleep-wakefulness regulation. Limitations in the available H2-receptor agonists and antagonists presently preclude a more detailed analysis of the role of H2-receptors on sleep and W.