We set out to determine the responses of macrophage migration inhibitory factor (MIF) to hepatic resection and investigate its role in predicting short-term postoperative morbidity and outcome. Blood samples from 29 patients undergoing hepatic resection and eight healthy volunteers were obtained serially for 24h and assayed for serum MIF, cortisol, and tumor necrosis factor (TNF)-alpha. The MIF and cortisol levels showed a parallel increase and their peak levels were significantly correlated (r2 = 0.33, P = 0.0011). The TNF-alpha levels also increased during and after hepatic resection, but did not correlate with the MIF levels. The patients were classified into an extended hepatectomy group (n = 9); a lobectomy/segmentectomy group (n = 12); and a subsegmentectomy group (n = 8). There were no differences in the time courses of MIF (P = 0.8699), cortisol (P = 0.7485), and TNF-alpha (P = 0.3819) among the three groups. No patients developed organ dysfunction and all were discharged from the intensive care unit without any complications. Our findings demonstrate that MIF production occurs in patients undergoing hepatic resection. Surgical stress may play a more important role in MIF secretion than inflammatory stimulus by TNF-alpha in these patients. Therefore, MIF minimally affects short-term postoperative morbidity and outcome.