It is known that slow breathing (<10 breaths min(-1)) reduces blood pressure (BP), but the mechanisms involved in this phenomenon are not completely clear. The aim of this study was to evaluate the acute responses of the muscle sympathetic nerve activity, BP and heart rate (HR), using device-guided slow breathing (breathe with interactive music (BIM)) or calm music. In all, 27 treated mild hypertensives were enrolled. Muscle sympathetic nerve activity, BP and HR were measured for 5 min before the use of the device (n=14) or while subjects listened to calm music (n=13), it was measured again for 15 min while in use and finally, 5 min after the interventions. BIM device reduced respiratory rate from 16+/-3 beats per minute (b.p.m) to 5.5+/-1.8 b.p.m (P<0.05), calm music did not affect this variable. Both interventions reduced systolic (-6 and -4 mm Hg for both) and diastolic BPs (-4 mm Hg and -3 mm Hg, respectively) and did not affect the HR (-1 and -2 b.p.m respectively). Only the BIM device reduced the sympathetic nerve activity of the sample (-8 bursts min(-1)). In conclusion, both device-guided slow breathing and listening to calm music have decreased BP but only the device-guided slow breathing was able to reduce the peripheral sympathetic nerve activity.