The sympathetic nervous system regulates the activity of a diverse range of target tissues through functionally specified efferent pathways. Since the earliest recordings of sympathetic nerves (Adrian et al. 1932) it has been known that many sympathetic outflows exhibit a pronounced, centrally generated, respiratory modulation of their activity (reviewed by (Habler et al. 1994)). In the specific case of the sympathetic control of the vasculature this respiratory modulation produces Traube-Hering waves, fluctuations in arterial pressure in phase with respiration. We have hypothesised that alterations in the strength of this respiratory-sympathetic coupling may be a causative factor in the development of hypertension. Previous work in the adult spontaneously hypertensive rat has reported changes in the phase relationship between respiration and sympathetic nerve activity (Czyzyk-Krzeska & Trzebski, 1990). We have extended these observations and find an enhancement of respiratory-sympathetic coupling in neonatal and juvenile spontaneously hypertensive rats, during the “pre-hypertensive phase” (see Simms et al. this meeting). This change in respiratory-sympathetic coupling occurs early in the development of elevated blood pressure, suggesting a potential causative link. At present, we have limited knowledge of the cellular and network interactions that produce the respiratory modulation of sympathetic activity at the level of the sympathetic preganglionic neurone (SPN). We have developed an approach allowing whole-cell patch clamp recordings from SPN in the neonatal rat working heart-brainstem preparation (Paton, 1996). This preparation generates robust central respiratory activity and shows characteristic respiratory modulated patterns of sympathetic output to that reported in vivo. Recordings from over 80 SPN in the upper thoracic spinal cord have shown several different patterns of respiratory modulation with either excitatory and/or inhibitory drives associated with the phases of the respiratory cycle. We have also functionally identified SPN on the basis of their responses to cardiorespiratory afferent activation e.g. peripheral chemoreflex, diving response and baroreceptor reflex. This has shown that some of these patterns of respiratory modulation are associated with different functional classes of SPN. For example putative muscle vascoconstrictor SPN, which play a key role in determining blood pressure, are predominantly excited in late inspiration/early expiration and inhibited in late expiration/early inspiration (Stalbovskiy et al. this meeting). From these data, we conclude that alterations in respiratory-sympathetic coupling appear to have a role in the development of hypertension and using in situ recordings we are able to examine the alterations in both inhibitory and/or excitatory respiratory drives to the muscle vasoconstrictor sympathetic preganglionic neurones, which are key determinants of arterial pressure.