Introduction The aim of the study was to evaluate the ability of different static and dynamic measurements of preload to predict fluid responsiveness in patients with spontaneous respiratory movements. Methods The subjects were 21 critically ill patients with spontaneous breathing movements receiving mechanical ventilation with pressure support mode (n = 9) or breathing through a face mask ( n = 12), and who required a fluid challenge. Complete hemodynamic measurements, including pulmonary artery occluded pressure ( PAOP), right atrial pressure ( RAP), pulse pressure variation (Delta PP) and inspiratory variation in RAP were obtained before and after fluid challenge. Fluid challenge consisted of boluses of either crystalloid or colloid until cardiac output reached a plateau. Receiver operating characteristics (ROC) curve analysis was used to evaluate the predictive value of the indices to the response to fluids, as defined by an increase in cardiac index of 15% or more. Results Cardiac index increased from 3.0 (2.3 to 3.5) to 3.5 (3.0 to 3.9) l minute(-1) m(-2) ( medians and 25th and 75th centiles), p < 0.05. At baseline, Delta PP varied between 0% and 49%. There were no significant differences in Delta PP, PAOP, RAP and inspiratory variation in RAP between fluid responders and non-responders. Fluid responsiveness was predicted better with static indices (ROC curve area +/- SD: 0.73 +/- 0.13 for PAOP, p < 0.05 vs Delta PP and 0.69 +/- 0.12 for RAP, p = 0.054 compared with Delta PP) than with dynamic indices of preload (0.40 +/- 0.13 for Delta PP and 0.53 +/- 0.13 for inspiratory changes in RAP, p not significant compared with Delta PP). Conclusion In patients with spontaneous respiratory movements, Delta PP and inspiratory changes in RAP failed to predict the response to volume expansion.