Animals anticipating a meal initiate a series of responses enabling them to better cope with the meal's metabolic impact. These responses, such as cephalic insulin, occur prior to the onset of ingestion and are especially evident in animals maintained on a meal-feeding schedule with limited but predictable access to food each day. We tested the hypothesis that meal-fed rats secrete the incretin hormone glucagon-like peptide-1 (GLP-1) cephalically when anticipating a large meal. Male Long-Evans rats were fed ad libitum (controls) or adapted to a schedule on which food was available for the same 4-h period each day (meal fed animals). Plasma GLP-1 increased in meal-fed rats over an interval from 75 to 60 min prior to feeding time, from a baseline of 10 to around 40 pm, and then returned to baseline prior to food presentation. Controls had steady plasma GLP-1 levels (10-15 pm) over the same span. Meal-fed rats also secreted cephalic insulin starting around 15 min prior to food presentation. Administration of the selective GLP-1 receptor antagonist exendin-4[desHis-1,Glu-9] prior to the premeal spike of GLP-1 caused meal-fed rats to eat significantly less food than normal, whereas administration of the antagonist after the GLP-1 spike but prior to food presentation resulted in a significant increase in food consumption. These findings document for the first time a cephalic increase of plasma GLP-1 and suggest that it functions to facilitate consumption of a large meal.