Two novel hypothalamic neuropeptides, orexin-A and -B, are suggested to regulate feeding. A single intracerebroventricular injection of orexin-A (23.4 nmol), administered 3 h into the light phase, increased feeding in satiated rats and prolonged feeding in fasted rats; it also increased feeding when given 6 h into, but not at the start of, the dark phase. An 8-day intracerebroventricular infusion with orexin-A (18 nmol/day) increased daytime feeding on days 2 and 8, but nocturnal feeding was reduced and there was no change in 24 h intake. Orexin-B had no effects. These results demonstrate a circadian variation in feeding responses to orexin-A.