Previous studies have demonstrated that dynamic cerebral autoregulation to spontaneous fluctuations in blood pressure is enhanced following lipopolysaccharide (LPS) infusion, a human experimental model of early sepsis, whereas by contrast it is impaired in patients with severe sepsis or septic shock. In this study, we hypothesized that this pattern of response would be identical during induced changes in blood pressure. Dynamic cerebral autoregulation was assessed in nine healthy volunteers and six septic patients. The healthy volunteers underwent a 4-h intravenous infusion of LPS (total dose: 2 ng kg(-1) ). Mean arterial blood pressure (MAP, arterial transducer) and middle cerebral artery blood flow velocity (MCAv, transcranial Doppler ultrasound) were recorded continuously during thigh-cuff deflation-induced changes in MAP for the determination of a modified rate of regulation (RoR). This was performed before and after LPS infusion in healthy volunteers, and within 72 h following clinical diagnosis of sepsis in patients. In healthy volunteers, thigh-cuff deflation caused a MAP reduction of 16 (13-20) % at baseline and 18 (16-20) % after LPS, while the MAP reduction was 12 (11-13) % in patients (P<0·05 versus volunteers at baseline; P<0·01 versus volunteers after LPS). The corresponding RoR values increased from 0·46 (0·31-0·49) s(-1) at baseline to 0·58 (0·36-0·74) s(-1) after LPS (P<0·05) in healthy volunteers, whereas they were similar to values observed in patients [0·43 (0·36-0·52) s(-1) ; P = 0·91 versus baseline; P = 0·14 versus LPS]. While our findings support the concept that dynamic cerebral autoregulation is enhanced during the very early stages of sepsis, they remain inconclusive with regard to more advanced stages of disease, because thigh-cuff deflation failed to induce sufficient MAP reductions in patients.