OBJECTIVE:: The administration of endotoxin to healthy humans reduces cerebral blood flow but its influence on dynamic cerebral autoregulation remains unknown. We considered that a reduction in arterial carbon dioxide tension would attenuate cerebral perfusion and improve dynamic cerebral autoregulation in healthy subjects exposed to endotoxemia. DESIGN:: Prospective descriptive study. SETTING:: Hospital research laboratory. SUBJECTS:: Ten healthy young subjects (age: 32 ± 8 yrs [mean ± SD]; weight: 84 ± 10 kg; weight: 184 ± 5 cm; body mass index: 25 ± 2 kg/m) participated in the study. INTERVENTIONS:: Systemic hemodynamics, middle cerebral artery mean flow velocity, and dynamic cerebral autoregulation evaluated by transfer function analysis in the very low (0.15 Hz) frequency ranges were monitored in these volunteers before and after an endotoxin bolus (2 ng/kg; Escherichia coli). MEASUREMENTS AND MAIN RESULTS:: Endotoxin increased body temperature of the subjects from 36.8 ± 0.4°C to 38.6 ± 0.5°C (p <.001) and plasma tumor necrosis factor-a from 5.6 (2.8-6.7) pg/mL to 392 (128-2258) pg/mL (p <.02). Endotoxemia had no influence on mean arterial pressure (95 [74-103] mm Hg vs. 92 [78-104] mm Hg; p = .75), but increased cardiac output (8.3 [6.1-9.5] L·min vs. 6.0 [4.5-8.2] L·min; p = .02) through an elevation in heart rate (82 ± 9 beats·min vs. 63 ± 10 beats·min; p <.001), whereas arterial carbon dioxide tension (37 ± 5 mm Hg vs. 41 ± 2 mm Hg; p <.05) and middle cerebral artery mean flow velocity (37 ± 9 cm·sec vs. 47 ± 10 cm·sec; p <.01) were reduced. In regard to dynamic cerebral autoregulation, endotoxemia was associated with lower middle cerebral artery mean flow velocity variability (1.0 ± 1.0 [cm·sec] Hz vs. 2.8 ± 1.5 [cm·sec] Hz; p <.001), reduced gain (0.52 ± 0.11 cm·sec.mm Hg vs. 0.74 ± 0.17 cm·sec.mm Hg; p <.05), normalized gain (0.22 ± 0.05 vs. 0.40 ± 0.17%·%; p <.05), and higher mean arterial pressure-to-middle cerebral artery mean flow velocity phase difference (p <.05) in the low frequency range (0.07-0.15 Hz). CONCLUSIONS:: These data support that the reduction in arterial carbon dioxide tension explains the improved dynamic cerebral autoregulation and the reduced cerebral perfusion encountered in healthy subjects during endotoxemia.