Male rats treated with reserpine were motionless and ingested only a few of ten consecutive intraoral injections of a 1 M solution of sucrose. While injection of apomorphine, a dopamine agonist, stimulated locomotion and stereotyped sniffing in reserpinized rats, it did not reactivate ingestive responses. The non-competitive N-methyl-D-aspartate receptor antagonist MK801, however, stimulated locomotion as well as ingestion suggesting involvement of glutamate in the suppressive effect of resperpine on ingestive responses. A series of experiments was therefore undertaken to investigate the possible physiological role of glutamate in feeding. For this purpose, we used Grill's intraoral intake test, in which the rat is infused intraorally with a sucrose solution and the amount ingested measured. In untreated rats, MK801 dose-dependently facilitated ingestion of the sucrose solution and antagonized inhibition of ingestion by cholecystokinin octapeptide. Administration of cholecystokinin octapeptide or ingestion of sucrose increased the concentration of glutamate in the nucleus of the solitary tract, a brain stem relay transmitting sensory information from the gastrointestinal tract to the forebrain. MK801 was found to bind specifically to this brain area and block the elevation of glutamate and dopamine levels which occurred after treatment with cholecystokinin octapeptide in this neural site. Together these data suggest that dopamine and glutamate may interact within the nucleus of the solitary tract in controlling ingestive behaviour.