We investigated the role of glutamatergic synapses in the expression of Fos protein at the nucleus tractus solitarii following baroreceptor activation in rats anaesthetized with pentobarbital sodium. Microinjection of L-glutamate (1 nmol) bilaterally into the nucleus tractus solitarii elicited significant hypotension and bradycardia. There was a concurrent increase, as determined immunohistochemically, in the expression of Fos protein at the commissural, medial and dorsomedial subnuclei of the caudal nucleus tractus solitarii. These effects were blunted when L-glutamate was co-administered with either the selective N-methyl-D-aspartate or non-N-methyl-D-aspartate glutamate receptor antagonist, dizocilpine maleate (200 pmol) or 6-cyano-7-nitroquinoxaline-2,3-dione (8 pmol), into the caudal nucleus tractus solitarii. Repeated and scheduled transient hypertension evoked by phenylephrine (2.5, 5.0 or 10.0 microg/kg, i.v.) also appreciably increased the number of Fos-immunoreactive neurons at the commissural, medial and dorsomedial subnuclei of the caudal nucleus tractus solitarii. The expression of Fos protein in this fashion was reduced, simultaneous with a discernible depression in baroreceptor reflex response, when baroreceptor activation was coupled with microinjection bilaterally of dizocilpine maleate (200 pmol) or 6-cyano-7-nitroquinoxaline-2,3-dione (8 pmol) into the nucleus tractus solitarii. Regression analysis showed that the depressive action on the baroreceptor reflex response by both glutamate receptor antagonists correlated positively to the reduction in Fos-immunoreactivity in the nucleus tractus solitarii after baroreceptor activation. Double immunohistochemical staining revealed that nucleus tractus solitarii neurons that showed Fos immunoreactivity were generally also immunoreactive to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor subunit 1. On the other hand, Fos immunoreactivity was usually absent from neurons in the nucleus tractus solitarii that were immunoreactive to N-methyl-D-aspartate receptor subunit 1. These results suggest that glutamatergic neurotransmission plays an active role, via comparable contributions from both N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors, in the expression of Fos protein at the caudal nucleus tractus solitarii in response to baroreceptor activation.