Dysbalance in the immune system is perceived as a major factor for adverse outcome after trauma. Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that regulates proliferation, differentiation of cells, wound healing, and angiogenesis. The influence of TGF-beta1 on trauma patients outcome is still unclear. Injury patterns and clinical outcome parameters of 99 consecutive patients with life-threatening injury and an injury severity score (ISS) > 15 were assessed in a prospective, single-center study at a Level I trauma center. Levels of TGF-beta1 in plasma were measured over a 5-day period by an enzyme-linked immunoabsorbant assay (ELISA). TGF-beta1 plasma levels rise shortly after trauma and gradually drop as the 5th day approaches. Mean and maximal TGF-beta1 plasma levels were significantly higher in patients who developed sepsis and were significantly lower in patients with renal or hepatic failure. Receiver operating characteristics-curve analysis of liver failure shows an area under the curve (AUC) of 0.68 (95%: 0.55-0.81, P = 0.02) and of an AUC of 0.63 (95%: 0.52-0.75, P = 0.03) for renal failure for maximal TGF-beta1 plasma (initial until day 2) levels if lower values represent a more positive test. The data indicate that the increase and decrease of TGF-beta1 plasma levels may contribute to clinical outcome after severe injury. Lower TGF-beta1 levels are associated with liver and renal insufficiency. Higher TGF-beta1 levels 6 h after ICU admission increase the risk of sepsis. TGF-beta1 seems to be an early onset reactant and not a second-line responsive cytokine.