Recent studies in this laboratory have shown an excitatory input from the arterial baroreceptors to vagal cardiomotor neurones in the medulla of the cat (McAllen & Spyer, 1978) and rabbit (Jordan, Khalid, Schneiderman & Spyer, 1979). The effectiveness of this input is determined by the excitability of these neurones which is controlled largely by an inhibitory influence exerted by inspiratory neurones, and possibly mediated by a cholinergic synapse (Garcia, Jordan & Spyer, 1978). Since in many circumstances where the baroreceptor-vagal reflex is modified, there is an accompanying change in respiratory activity, it was important to investigate the extent to which inspiratory drive might be the determining factor in all such conditions.In anaesthetized cats (z-chloralose, 70 mg/kg i.v.) and rabbits (urethane 1.5 mg/kg I.v.) the activity of vagal preganglionic neurones in the medulla was recorded via one barrel of a multi-barrelled micropipette. The influence of hypothalamic stimulation on vagal activity was studied at sites from which marked cardiovascular changes are evoked.In the rabbit, stimulation at 'pressor' sites evoked variable changes in heart rate although usually an initial tachycardia. By constructing post-stimulus histograms of vagal unit activity during hypothalamic stimulation (0 1 msec pulses, < 150 flA at 2 Hz) an inhibitory influence was revealed which was often manifest within 10 msec.In the cat, stimulation within the hypothalamic defence area evoked a similar change in vagal activity, this inhibitory influence being apparent for up to 200 msec. Further, the excitatory response of vagal neurones to aortic nerve stimulation (a 500 Hz train of three pulses delivered repetitively at < 2 Hz) was suppressed by a conditioning stimulus delivered to the hypothalamus 20-150 msec earlier.We have tested whether this suppression can be explained as a consequence of an enhanced inspiratory drive. Since the inhibition of vagal activity during inspiration is blocked by ionophoretically applied atropine (Garcia et al. 1978), we have investigated its effect on the inhibitory influence of hypothalamic stimulation. Although in the present study acetylcholine applied ionophoretically inhibited vagal discharge (neurones were firing in response to DL-homocysteic acid) and this was antagonized by atropine, atropine had no effect on hypothalamically evoked inhibition. Equally the suppression of the baroreceptor input to these neurones seen during hypothalamic stimulation was unaffected.These data suggest that vagal cardiomotor neurones are under at least two distinct inhibitory controls. There is an inhibitory input to vagal neurones from the hypothalamus which is independent of inspiratory-mediated inhibition. Where hypothalamic stimulation evokes an enhanced inspiratory drive, it is likely that both inhibitory processes contribute to the suppression of the baroreceptor-vagal reflex.