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Transient declines in blood glucose concentration are proposed to be signals that induce meal initiation in free-feeding rats. This assertion is based upon the following evidence: (1) the observation that a transient declines in blood glucose preceded each meal; (2) attenuation of transient decline in blood glucose by i.v. glucose led to a delay in meal initiation; (3) declines in blood glucose were endogenous and that if access to food was denied during and after a decline in blood glucose and then restored, meal initiation was not observed until after another transient decline; (4) experimental induction of transient declines in blood glucose that mimic the pattern of blood glucose prior to spontaneous meals resulted in meal initiation; (5) a transient spike of insulin was observed just prior to the transient decline in blood glucose that precedes meal initiation; (6) in rats with total subdiaphragmatic or hepatic vagotomy, normal transient declines in blood glucose occurred but meal initiation was observed only after approximately 55 percent of the declines; (7) since infusions of other substrates (amino acids, ketone bodies, hexoses) failed to delay or block meal initiation, this signal appears to be specific for glucose. These studies, conducted in our laboratories over the past five years, suggest that transient declines in blood glucose with the necessary shape and magnitude are reliable signals for feeding that are detected by central nervous system glucose receptive elements and are mapped into meal initiation.