Central command is a feedforward neural mechanism that evokes parallel modifications of motor and cardiovascular function during arousal and exercise. The neural circuitry involved has not been elucidated. We have identified a cholinergic neural circuit that, when activated, mimics effects on tonic and reflex control of circulation similar to those evoked at the onset of and during exercise. Central muscarinic cholinergic receptor (mAChR) activation increased splanchnic sympathetic nerve activity (SNA) as well as the range and gain of the sympathetic baroreflex via activation of mAChR in the rostral ventrolateral medulla (RVLM) in anesthetized artificially ventilated Sprague–Dawley rats. RVLM mAChR activation also attenuated and inhibited the peripheral chemoreflex and somatosympathetic reflex, respectively. Cholinergic terminals made close appositions with a subpopulation of sympathoexcitatory RVLM neurons containing either preproenkephalin mRNA or tyrosine hydroxylase immunoreactivity. M2 and M3 receptor mRNA was present postsynaptically in only non–tyrosine hydroxylase neurons. Cholinergic inputs to the RVLM arise only from the pedunculopontine tegmental nucleus. Chemical activation of this region produced increases in muscle activity, SNA, and blood pressure and enhanced the SNA baroreflex; the latter effect was attenuated by mAChR blockade. These findings indicate a novel role for cholinergic input from the pedunculopontine tegmental nucleus to the RVLM in central cardiovascular command. This pathway is likely to be important during exercise where a centrally evoked facilitation of baroreflex control of the circulation is required to maintain blood flow to active muscle.