BACKGROUND Oxygen-derived free radicals have been implicated in the pathogenesis of lung injury and endothelial dysfunction after cardiopulmonary bypass (CPB). We examined the effects of priming the CPB pump with a low-molecular-weight hydroxyethyl starch pentastarch (PS) solution, PS conjugated to the iron chelator deferoxamine (DFO), or lactated Ringer's solution alone (LR) on lung injury parameters and skeletal microvessel relaxation responses. RESULTS Sheep were placed on hypothermic CPB with a prime of PS (n = 8), PS-DFO (n = 8), or LR (n = 8). A 60-minute period of cardioplegia-ischemia was followed by rewarming, separation from CPB, and 2 hours of post-CPB monitoring. Hemodynamics, oxygenation, pulmonary lymph flow, lymph protein clearance, and total body weight were measured. Right and left atrial blood samples were obtained simultaneously for white blood cell and platelet counts. No statistically significant hemodynamic or oxygenation differences were found between groups. Lymph flow was increased after CPB but significantly more in the LR group (264.6 +/- 45%, P < .05) compared with PS-DFO (126.6 +/- 22%) or PS (120.9 +/- 25%). Increases in lymph protein clearance and weight gain were significantly less with PS and PS-DFO compared with LR (P < .05). CONCLUSIONS The oncotic agent PS ameliorates lung derangements seen after CPB compared with that seen with an LR prime, and no significant additional pulmonary benefit was demonstrated with PS conjugated to the oxygen-derived free radical scavenger DFO.