The possible role of L-glutamic acid (L-glu) as a neurotransmitter of baroreceptor afferent neurons was investigated in the cat by monitoring the changes in three indices of baroreceptor function seen with the L-glu antagonists L-glutamic acid diethyl ester (GDEE) and 1-hydroxy-3-amino-pyrrolidone-2-(HA-966). Baroreceptor function was determined from a) the computer summed inhibition of sympathetic nerve discharge (SND) evoked by electrical stimulation of vagal baroreceptor afferent pathways, b) the locking of SND to the cardiac cycle, and c) the sympathoinhibitory response to i.v. pressor doses of phenylephrine. Direct bilateral microinjections of GDEE (20 micrograms) and HA-966 (4 micrograms) into the region of the nucleus tractus solitarii (NTS) resulted in immediate, marked reductions in the SND inhibitory response to vagal stimulation, a loss in SND locking to the cardiac cycle, a shift in the arterial pulse/SND phase relation, and a diminished sympathoinhibitory response to phenylephrine. Control microinjections of isotonic saline (1 mu 1/NTS) were devoid of these effects. The vagal induced sympathoinhibitory response was restored after NTS microinjections of GDEE by increasing the intensity of the vagal stimulus, or by directly stimulating the NTS injection site, suggesting that the impairment in baroreceptor function seen with this L-glu antagonist was independent of mechanical or local anesthetic effects. These data strongly suggest that L-glu may act as a neurotransmitter of baroreceptor afferent neurons in the NTS of the cat.