The histamine synthesis inhibitor a-fluoromethylhistidine (a-FMH, 50 mg/kg, i.p.) significantly reduced wakefulness (W) and light sleep and increased slow wave sleep (SWS) and REM sleep during the light period in rats housed under 12 h light/12 h dark conditions (12L/12D). When animals were housed under 16 h light/8 h dark (16L/8D) they remained awake for a longer period of time during the dark as compared to the 12L/12D lighting cycle. Under this condition a-FMH 50 mg/kg significantly decreased W and increased SWS. Our results tend to indicate that histamine intervenes in sleep-wakefulness regulation. In addition, histamine could be partly involved in the abnormally increased incidence of W observed during the dark in rats housed under 16L/8D conditions.