This study investigates whether ethanol affects the cardiovascular changes evoked by the excitatory amino acid glutamate in the nucleus of the solitary tract (NTS). Male Sprague-Dawley rats were anesthetized with urethane and instrumented for microinjection of drugs into the NTS. In 28 animals, an initial dose-response curve for glutamate (37, 74, and 148 pmol/60 nL) was obtained. In eight animals (control group), the dose-response curve was unchanged when it was tested after microinjection of 60 nL of saline into the NTS. In contrast, the prior intra-NTS administration of ethanol (25 or 50 mM) consistently inhibited the hypotensive and bradycardic effects of glutamate. The specificity of this inhibitory response was corroborated by the inability of intra-NTS administrations of ethanol (50 mM) to affect the hypotensive and bradycardic responses to nicotine (922 pmol, 1.84 nmol, and 3.96 nmol). These results indicate that the cardiovascular effects of glutamate can be antagonized by ethanol in the NTS. This inhibitory effect, in turn, may provide a basis for the hypertensinogenic action of ethanol in humans.