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Respiratory-related variabilities in stroke volume and arterial pulse pressure (Δ%Pp) are proposed to predict fluid responsiveness. We investigated the influence of tidal volume (Vt) and adrenergic tone on these variables in mechanically ventilated patients. Cyclic changes in aortic velocity–time integrals (Δ%VTIAo, echocardiography) and Δ%Pp (catheter) were measured simultaneously before and after intravascular volume expansion, and Vt was randomly varied below and above its basal value. Intravascular volume expansion was performed by hydroxyethyl starch (100 mL, 60 s). Receiver operating characteristic curves were generated for Δ%VTIAo, Δ%Pp and left ventricle cross-sectional end-diastolic area (echocardiography), considering the change in stroke volume after intravascular volume expansion (≥15%) as the response criterion. Covariance analysis was used to test the influence of Vt on Δ%VTIAo and Δ%Pp. Twenty-one patients were prospectively included; 9 patients (43%) were responders to intravascular volume expansion. Δ%VTIAo and Δ%Pp were higher in responders compared with nonresponders. Predictive values of Δ%VTIAo and Δ%Pp were similar (threshold: 20.4% and 10.0%, respectively) and higher than that of left ventricle cross-sectional end-diastolic area at the appropriate level of Vt. Δ%Pp was slightly correlated with norepinephrine dosage. Δ%Pp increased with the increase in the level of Vt both before and after intravascular volume expansion, contrasting with an unexpected stability of Δ%VTIAo. In conclusion, Δ%VTIAo and Δ%Pp are good predictors of intravascular fluid responsiveness but the divergent evolution of these two variables when Vt was increased needs further explanation.