When neuropeptide Y (NPY) is administered centrally, meal-anticipatory responses are elicited. If an increase of endogenous NPY is a signal that heralds an imminent large caloric load, timed daily NPY injections may be expected to condition meal-anticipatory responses that facilitate ingestion. Rats received 4-h access to food beginning in the morning and then timed (1600 h), daily third-ventricular injections of NPY or saline for 7 days. On test day (day 8), animals received the conditioning drug (NPY or saline) or the opposite drug. Food was available immediately after injection on test day, and intake was measured. Rats conditioned with NPY and then given saline ate significantly more than rats conditioned with saline and then given saline; they ate the same amount as rats given NPY. Although they ate more, rats trained with NPY did not have changed plasma glucose, insulin, or ghrelin. These data suggest that NPY plays a role in mediating conditionable food-anticipatory responses that help to cope with the effects of large caloric loads.