Angiogenesis is a key component of the repair mechanisms triggered by tissue injury. Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis, as it acts directly and specifically on endothelial cells. VEGF produced locally in regenerating tissue may spill over into the systemic circulation, and measuring levels of circulating VEGF may allow monitoring of angiogenesis. To determine whether circulating VEGF is increased after severe injury, we measured concentrations of VEGF in serial serum samples of 23 mechanical burn patients, 55 patients with multiple trauma and 56 healthy normal controls, using a newly established ELISA assay. In burn patients, serum VEGF was increased on day 1 (369.4 ± 88.0 pg/ml) and on day 3 (452.0 ± 65.3 pg/ml), reached highest levels on day 14 (1809.5 ± 239.7 pg/ml) and was still elevated on day 21 post-burn (1339.8 ± 208.7 pg/ml) (mean ± SEM, p<0.01), when compared with healthy controls (82.2 ± 10.8 pg/ml (mean ± SEM)). Likewise, in trauma patients, serum VEGF showed a trend towards elevated values on the day of admission (186.9 ± 43.9 pg/ml) and on day 3 after injury (193.2 ± 62.1 pg/ml). Thereafter, serum VEGF increased further (day 7, 507.0 ± 114.7 pg/ml), peaked on day 14 (742.4 ± 151.8 pg/ml) and was still elevated on day 21 after injury (693.1 ± 218.6 pg/ml (mean ± SEM, p<0.01)). No significant correlation was observed between peak serum VEGF and initial severity of mechanical (Injury Severity Score) or burn injury (percentage of body surface burned). However, in both burn and trauma patients, the subgroup of patients with uncomplicated healing showed significantly higher increases of serum VEGF than the subgroup who developed severe complications during the post-traumatic course, such as sepsis, adult respiratory distress syndrome or multiple organ failure (p<0.05). Thus, markedly enhanced levels of serum VEGF are present one to three weeks after trauma or burn injury. Further, occurrence of severe complications during the post-traumatic period is associated with lesser increases of serum VEGF.