There is increasing evidence that the parabrachial nucleus (PBN) may be integrally involved in cardiovascular reflex regulation. In cats in which anesthesia was induced with pentobarbital and maintained with α-chloralose, we studied the effects of PBN stimulation on cardiovascular afferent inputs to nucleus tractus solitarius (NTS), the site of first central termination for cardiovascular afferent fibers. Electrical stimulation of PBN resulted in an initial excitation followed by prolonged inhibition of the spontaneous activity of NTS neurons activated by ipsilateral carotid sinus nerve (CSN) stimulation. In 53 units recorded extracellularly in and around NTS, the number of action potential responses to ipsilateral CSN stimulation was reduced 73 ± 3% by a prior conditioning stimulus to PBN at an interval of 30-60 msec. CSN input to 10 units excited by selective baroreceptor stimulation was inhibited by the PBN conditioning stimulus, as were convergent inputs from contralateral CSN, vagus, and renal nerves. The inhibitory influence of the PBN stimulus lasted as long as 450 msec. We examined the mechanism for these phenomena in additional intracellular recording experiments. In 57 units, PBN stimulation evoked a long lasting (65-359 msec) membrane potential hyperpolarization. In 42 cells, the PBN evoked inhibitory postsynaptic potential (IPSP) was preceded by an excitatory postsynaptic potential (EPSP). CSN and convergent inputs were inhibited when timed to occur during the PBN induced IPSP. Conversely, CSN and convergent afferent nerves inhibited PBN input to NTS neurons with no associated change in membrane potential (n = 9 of 14). These data demonstrate for the first time a potent modulatory influence of PBN on NTS neurons processing cardiovascular afferent input.