Arousals from sleep can be associated with increases in blood pressure (BP). However, it is uncertain whether this is due to a direct effect of arousals on BP, or is secondary to respiratory stimuli present at the time of the arousal. Cheyne-Stokes respiration (CSR) in patients with congestive heart failure (CHF) provides unique conditions that may allow these two possibilities to be distinguished. In CSR, the apnea-hyperpnea cycle can be dissociated from arousals because when CSR occurs during wakefulness, it does so in the absence of arousals, and when it occurs during sleep, arousals occur either at the termination of apnea (early arousals) or several breaths after the onset of hyperpnea (late arousals). We therefore measured BP during wakefulness and non-rapid eye movement (NREM) sleep in eight patients with CHF and CSR. During wakefulness, CSR was associated with wide fluctuations in systolic BP (mean +/- SD, 11.3 +/- 6.0 mm Hg) synchronous with the apnea-hyperpnea cycle, in the absence of arousals. Similar fluctuations in BP were observed during CSR with early arousals (13. 7 +/- 7.0 mm Hg) in NREM sleep. However, late arousals during CSR were associated with a small, but significant additional effect on systolic BP (14.2 +/- 7.1 mm Hg, p < 0.05). Furthermore, the degree of BP increase following arousals was directly related to the associated increase in ventilation (r = 0.70, p < 0.05). We conclude that BP fluctuations during CSR in patients with CHF are primarily related to oscillations in ventilation during the CSR cycle and can occur in the absence of arousals. Arousals augment these BP oscillations, but only when they occur late in hyperpnea.