Positive end-expiratory pressure (PEEP) has been shown to cause a depression of mesenteric blood flow (MBF) and redistribution of blood flow away from the mesenteric vascular bed. Objective: We sought to determine whether two commonly used vasoactive agents, dopamine, a known mesenteric vasodilator and inotrope, and dobutamine, with its inotropic properties, would correct the MBF depression caused by PEEP. Design, Material, and Methods: Sprague-Dawley rats, 180 to 250 g, were treated with mechanical ventilation and either no PEEP (control group) or increasing levels (0, 10, 15, and 20 cm of H2O pressure) of PEEP (PEEP group). Also, we evaluated PEEP's effect on MBF and cardiac output (GO) under the influence of a continuous infusion of 2.5 or 12.5 mu g/kg/min of dopamine or 2.5 or 12.5 mu g/kg/min of dobutamine, Cardiac output and, using in vivo videomicroscopy, mesenteric Al, A2, and A3 arteriolar intraluminal radii and Al arteriolar optical Doppler velocities were measured. After 20 cm of H2O pressure PEEP was attained, two boluses of 2 mt of 0.9 normal saline were given. The MBF was calculated from vessel radius and red blood cell velocity, Measurements and Main Results: There were no significant changes from baseline in mean arterial pressure or A2 or A3 diameters in any of the groups. Both MBF and CO were unchanged over time in the control group. The MBF was reduced 78% (p < 0.05) and the CO was reduced 31% (p < 0.05) from baseline at 20 cm of H2O pressure PEEP. After 4 mt of normal saline, the MBF was still 53% below baseline (p < 0.05), while the CO had returned to baseline in the PEEP group. Low-dose dopamine partially ameliorated both the decrease in CO and MBF caused by PEEP, but 4 mt of normal saline was required in addition to the low-dose dopamine to return MBF to baseline levels while on 20 cm of H2O pressure PEEP. High-dose dopamine with the addition of 4 mt of normal saline returned CO to baseline on 20 cm of H2O pressure PEEP, but MBF remained approximately 46% below baseline despite fluid boluses. Neither low-dose nor high-dose dobutamine, with or without fluid boluses, had an appreciable positive effect on CO or MBF. Conclusions: It is clear that inotropes are not a replacement for adequate fluid loading to correct the depression in cardiac output and mesenteric blood now associated with the use of mechanical ventilation and PEEP. Low-dose dopamine may serve as an adjunct to adequate fluid resuscitation to improve MBF.