Severe congestive heart failure (CHF) is associated with Cheyne-Stokes (C-S) respiration, which may be an index of poorer prognosis. The mechanisms linking C-S respiration to poorer functional status and prognosis in patients with CHF are unknown. We tested the hypothesis that C-S respiration increases muscle sympathetic nerve activity (MSNA) in 9 patients with CHF. Oxygen saturation was 96 +/- 1% during normal breathing and 91 +/- 1% after the apneic episodes (p < 0.05). Mean blood pressure was 79 +/- 8 mm Hg during normal breathing and 85 +/- 8 mm Hg during C-S respiration (p = 0.001). C-S respiration increased MSNA burst frequency (from 45 +/- 5 bursts/min during normal breathing to 50 +/- 5 bursts/min during C-S respiration; p < 0.05) and total integrated nerve activity (to 117 +/- 7%; p < 0.05). We also studied an additional 5 patients in whom C-S breathing was constant, without any periods of spontaneous normal breathing. In these patients, MSNA was higher (65 +/- 5 bursts/min) than MSNA in patients in whom C-S breathing was only intermittent (45 +/- 5 bursts/min; p < 0.05). In all 14 patients, the effects of different phases of C-S respiration were examined. MSNA was highest during the second half of each apnea (increasing to 152 +/- 14%; p < 0.01) and blood pressure was highest during mild hyperventilation occurring after termination of apnea (p < 0.0001). We conclude that C-S respiration decreases oxygen saturation, increases MSNA, and induces transient elevations in blood pressure in patients with CHF.