Arterial pressure exhibits rhythmic fluctuations with the respiratory cycle (Traube-Hering Waves; THW). These have been attributed to cyclical alterations in intrathoracic pressure and venous return affecting cardiac output. An alternative view posits that they are due to central coupling between the sympathetic and respiratory pattern generators, as sympathetic vasomotor activity is respiratory-modulated. This is pertinent, as increased respiratory-sympathetic coupling has been linked with hypertension (Simms et al 2009). We used microneurography to explore this hypothesis in man. Methods: 6 healthy, normotensive males (age 21-30) had muscle sympathetic nerve activity (MSNA) recordings from the peroneal nerve alongside continuous arterial pressure, ECG and respiratory thoracic excursion. Recordings were made at rest, during fixed frequency (ff-) breathing and with 5cmH2O positive end-expiratory pressure (PEEP). Respiratory-triggered averages of MSNA and mean arterial pressure (MAP) defined the magnitude and phase relationships of the THW and MSNA bursts. This was used to collect a breath-by-breath time series of thoracic excursion, ΔMAP and integrated MSNA. Data are expressed as means±SEM, significance tested using ANOVA or t-tests (p<0.05) and relationships explored with linear regression and cross correlation. Results: All 6 subjects showed THW (1.9±0.3mmHg), with a latency of 2.7±0.2s after end inspiration (resting conditions, p<0.005). THW amplitude was not changed by ff-breathing but was increased to 4.7±0.2mmHg (p=0.04, n=6, ANOVA) by addition of PEEP. Significant respiratory-related bursts of MSNA were observed in all subjects. The sympathetic burst started 1.2±0.3s prior to end inspiration and end 0.9±0.4s after. The addition of PEEP tended to increase MSNA bursts amplitude and shift its phase. The magnitude of the respiratory-related MSNA correlated positively (p<0.01) with the amplitude of the following THW in 1 subject at baseline, in 3 subjects during paced breathing and this was strengthened by the addition of PEEP. In contrast, amplitude of the preceding THW did not predict the magnitude of the MSNA burst. There were also positive correlations (p<0.05;n=4) between the amplitude of thoracic excursion and that of the following THW, most prominent at baseline. Thoracic excursion did not correlate with MSNA amplitude. Conclusion: Amplitude domain analysis of MSNA in man reveals respiratory-sympathetic coupling. Time domain analysis shows predictive correlations between sympathetic burst strength and the following THW amplitude (not vice versa) suggesting a causal relationship that can be strengthened by application of PEEP, a manoeuvre that may increase central respiratory drive. This lends weight to the hypothesis that THW are the product of central respiratory-sympathetic coupling.