The effects of 46 h of mechanical ventilation and PEEP on urinary output, sodium excretion, and renal and cardiovascular function were examined. Dogs sedated with sodium pentobarbital were ventilated using one of three modes: spontaneous ventilation (SV), controlled mechanical ventilation (CMV), or CMV with 10 cmH2O positive end-expiratory pressure (CMV with PEEP). Intravenous fluids were given at a constant rate throughout the study and measurements of renal and cardiovascular function were made over four periods. Dogs whose lungs were ventilated with PEEP displayed more than two times the amount of fluid retention seen in the other groups as assessed by mean weight gain. This was due to an initial depression of urine flow, sodium excretion, and free water clearance. Urinary flow rate approximated the rate of fluid infusion by 20 h in SV dogs and by 27 h during CMV, while the maximum during CMV with PEEP occurred at 46 h. There were no significant differences in glomerular filtration rate, renal corticomedullary blood flow distribution, or renal blood flow between groups. During the 46 h, cardiac index increased (SV, +16%; CMV, +19%; CMV with PEEP, +64%), while systemic vascular resistance (SV, –28%; CMV, –30%; CMV with PEEP, –57%), renal vascular resistance (SV, –12%; CMV, –20%; CMV with PEEP, –23%), and mean arterial pressure (SV, –16%; CMV, –15%; CMV with PEEP, –15%) decreased in all groups. This study has demonstrated that when a constant sodium and water load was provided, the SV and CMV groups were rapidly able to adjust the urinary excretion to meet input, while the return of renal function toward normal in the CMV with PEEP group was delayed until almost 46 h from the start of ventilation.