Sympathetic preganglionic neurons (SPN) represent the final central neurons in the sympathetic pathways which regulate vasomotor tone; they therefore play a pivotal role in the re-distribution of cardiac output to different vascular beds in response to environmental challenges. While the consensus view is that activity in these neurons is due mainly to supraspinal inputs, the possibility that some activity may be generated intrinsically and modified by synaptic inputs cannot be excluded. Therefore, in order to distinguish between these two possibilities, the electrophysiological properties of cardiovascular-like SPN in the upper thoracic spinal cord of the anesthetized rat were examined and their response to activation of vasodepressor inputs was investigated. Intracellular recordings were made from 22 antidromically identified SPN of which 17 displayed irregular, but maintained, spontaneous activity; no evidence of bursting behavior or pacemaker-like activity was observed. Stimulation of the aortic depressor nerve or a vasodepressor site within the nucleus tractus solitarius (NTS) resulted in a membrane hyperpolarization, decrease in cell input resistance and long-lasting cessation of neuronal firing in SPN including a sub-population which had cardiac-modulated patterns of activity patterns. Recordings were also undertaken from 80 non-antidromically-activated neurons located in the vicinity of SPN; 23% of which fired in phase with the cardiac cycle, with this peak of activity occurring before similar increases in cardiac-modulated SPN. Stimulation of vasodepressor regions of the NTS evoked a membrane hyperpolarization and decrease in cell input resistance in cardiac-modulated but not non-modulated interneurons. These studies show that activity patterns in SPN in vivo are determined principally by synaptic inputs. They also demonstrate that spinal interneurons which exhibit cardiac-modulated patterns of activity are postsynaptically inhibited following activation of baroreceptor pathways. However, the question as to whether these inhibitory pathways and/or disfacilitation of tonic excitatory drive underlies the baroreceptor-mediated inhibition of SPN remains to be determined.