Background: Arginine metabolism and availability after surgery or trauma (ST) is an important modulator of immune responses. Arginine levels are significantly depleted in human trauma patients. Diets containing arginine administered to surgery patients have restored immune function. We hypothesized an arginase-dependent depletion of arginine in a murine model of ST. In addition, we hypothesized a systemic arginase release in human trauma patients. Methods: Male mice were anesthetized and a laparotomy with bowel manipulation was used as a model of ST. Plasma was collected after ST for analysis of arginase activity and arginine, ornithine, and citrulline. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in plasma were measured after ST. Also, arginase activity was determined in human plasma from 4 healthy controls and 8 trauma patients. Results: Arginase activity increased maximally at 2-4 hours after ST, and arginine was significantly reduced after ST. Citrulline was significantly decreased at 8 and 12 hours after ST. Plasma AST and ALT did not significantly vary from control mice after ST. In addition, on day 1 after intensive care unit admission, human trauma patients exhibited a significant increase in arginase activity. Conclusions: The biological consequences of arginine depletion remain incompletely understood. These data are consistent with data showing that patients given arginine-containing diets experience reduced morbidity. Understanding of arginine metabolism after ST may lead to therapies aimed at improving clinical outcome after ST.