Tumor necrosis factor (TNF) and interleukin 6 (IL-6) are purported to be important mediators of inflammatory responses. It is not known whether the plasma levels of these cytokines are altered after trauma and hemorrhage. Our objectives were to determine whether there is any elevation of plasma TNF or IL-6 after trauma and hemorrhage and to what extent these changes are due to tissue trauma vs. simple hemorrhage. Trauma was induced in Sprague-Dawley rats under light ether anesthesia by performing a 5-cm midline laparotomy. On closure, animals were catheterized, awakened, hemorrhaged to a mean blood pressure of 40 mmHg, and maintained at that pressure until 40% of maximum shed blood volume was returned in the form of Ringer lactate (RL). Animals were then resuscitated with RL equivalent to four times shed blood volume. Blood samples (0.5 ml) were taken before inducing hemorrhage, at maximal bleed out (45 min), and at 4 and 6 h posthemorrhage to obtain plasma. IL-6 and TNF levels were measured using cytokine-dependent cellular assays. TNF levels were significantly elevated at 45 min into hemorrhage and remained so up to 4 h after hemorrhage. IL-6 levels were also elevated 45 min into hemorrhage and remained so up to 6 h posthemorrhage. IL-6, unlike TNF, was already significantly increased after midline laparotomy and before initiation of hemorrhage compared with unmanipulated animals. Thus induction of IL-6 by trauma may be partially independent of those mechanisms in hemorrhage that are involved in the release of TNF.