In vivo microdialysis was employed to measure release of endogenous L-glutamate (GLU) and L-aspartate (ASP) in the medial nucleus tractus solitarius of urethane anaesthetised rats. Basal extracellular levels of these amino acids were stable following a 90 min equilibration period (6.3 +/- 0.24 and 3.4 +/- 0.6 pmol/20 microliters sample of GLU and ASP, respectively). Basal levels of endogenous extracellular GLU and ASP were increased over 2-fold and 3-fold, respectively, following local administration of the selective 5-hydroxytryptamine (5-HT3) receptor agonist phenylbiguanide (300 microM). Intracerebral administration of the selective 5-HT3 receptor antagonist ondansetron (30 microM) blocked the effect of phenylbiguanide on GLU release whilst the effect on ASP was variable and complex. These data suggest that 5-HT3 receptor activation in the rat nucleus tractus solitarius can affect excitatory amino acid neurotransmission in this region of the medulla oblongata.