Cats were chronically implanted with electrodes for polygraphic recordings and cannulae for intracerebral microinjections in order to study the functional role of histaminergic innervation of the preoptic-anterior hypothalamus in sleep-wake control. α-Fluoromethylhistidine (αFMH, 50 μg in 1 μl), a specific inhibitor of the histamine-synthesizing enzyme, when injected bilaterally into the preoptic area, where numerous histaminergic fibres and terminal-like structures are present, caused a significant increase in deep slow wave sleep (S2) and paradoxical sleep (PS) and a decrease in wakefulness. In contrast, microinjections of histamine (5 or 30 μg in 1 μl) in the same area dose-relatedly increased wakefulness and decreased both slow wave sleep and paradoxical sleep. The effects of histamine were reduced by pretreatment with mepyramine (1 mg/kg i. p.), a well known histamine H1 receptor antagonist, and were mimicked by a local injection of impromidine (1 μg in 1 μl), a potent histamine H2 receptor agonist. Microinjections of mepyramine alone (120 μg in 1 μl) caused an increase in slow wave sleep. These results suggest that preoptic histaminergic innervation is involved in sleep-wake control and that the action might be mediated via both H1 and H2 receptors.