Since the earliest direct recordings, it has been known that sympathetic nerve activity (SNA) shows respiratory modulation. During normal breathing in healthy humans, sympathetic vasoconstrictor outflow to the vasculature of the skeletal muscle reaches a nadir at peak inspiration and peaks during expiration (Dempsey et al. 2002). Notably, recent work has suggested that altered respiratory-sympathetic coupling is a causal factor in producing the increased vascular resistance and blood pressure (BP) in the spontaneously hypertensive rat (Simms et al. 2009). The aim of the present study was to begin to elucidate the respiratory modulation of muscle SNA in human hypertension. Ten hypertensive patients (62±2 years; body mass index [BMI] 27±1 kg/m2; mean ± S.E.M.; 5 men) and six age and BMI matched normotensive control subjects (59±2 years; BMI 27±2 kg/m2; 2 men) rested in a supine position, breathing at a eupnoeic frequency, while heart rate (HR; ECG), arterial BP (automated sphygmomanometry and finger photoplethysmography) and respiratory movements (strain gauge pneumobelt) were continuously monitored. Multiunit recordings of postganglionic muscle SNA were obtained from the peroneal nerve using the microneurography technique. To examine respiratory-sympathetic modulation, respiratory and muscle SNA signals were first normalised to unit variance and mean-removed, followed by calculation of the cross-correlation function. This resulted in a correlation coefficient (i.e., r value) varying between 1 and -1. A peak (or trough) at positive time lag indicates respiration leading the muscle SNA signal. Cross correlations were averaged across subjects, allowing for calculation of S.E.M. and 95% confidence intervals. As expected, mean BP was higher in hypertensive group (114±4 vs. 83±3 mmHg, hypertensives vs. control; P<0.05). In contrast, HR (62±3 vs. 67±7 beats/min-1) and muscle SNA (57±4 vs. 54±7 bursts/100 heartbeats-1) were similar in the hypertensive and control groups (P>0.05). In the control group, the cross correlation function displayed a significant negative r value of -0.16±0.02 at positive lag of 538 ms, indicative of an inhibitory effect of respiration on muscle SNA. In the hypertensive group, this inhibitory relationship was significantly attenuated (P<0.05; r value 0.01±0.03 at positive lag of 636 ms). These preliminary data indicate that the inhibitory effect of respiration on muscle SNA is suppressed in older patients with hypertension. Further studies are required to elucidate the underlying mechanisms and in particular the potential changes in peripheral afferent feedback versus central modulation.