In vivo microdialysis was employed to measure release of endogenous L-glutamate and L-aspartate in the region of the dorsomedial medulla oblongata including the medial nucleus tractus solitarius of the anaesthetized rat. Basal extracellular levels of these amino acids were stable and increased over two-fold when the perfusate was changed to a high KCl (80 mM) artificial cerebrospinal fluid. This high K(+)-evoked release was calcium-dependent, while basal levels were insensitive to removal of calcium ions from the perfusate. An intravenous infusion of phenylephrine, which elevated blood pressure, caused a marked increase of both spontaneous and evoked release of glutamate. In contrast aspartate efflux was not significantly altered. The present data provide evidence that the excitatory amino acids, glutamate and aspartate, serve a neurotransmitter function in the nucleus tractus solitarius of the rat. Furthermore, the increase in glutamate release following baroreceptor activation with phenylephrine suggests that glutamate may be a neurotransmitter at baroreceptor afferent nerve terminals within the nucleus tractus solitarius. On the other hand, aspartate appears to be possibly an inter-neuronal transmitter in this brain region.