Previous studies in critically ill patients have shown the beneficial effects of early enteral nutrition supplemented with arginine, omega-3 fatty acids and nucleotides (Impact) on immunological response, infection rate and length of stay in hospital. No specific data exist for patients with severe multiple injury, who represent a high risk group for systemic inflammatory response syndrome (SIRS), septic complications and multiple organ failure (MOF). In this prospective, randomized, double-blind controlled clinical study on patients after severe trauma (ISS ca. 40) the primary study endpoints were incidence of SIRS and MOF [definitions according to Am Soc Grit Care Med (5) and Goris (23), Sauaia (43)]. Thirty-two patients enrolled in the study, and 29 were eligible for analysis: test (Impact) (n = 16), control (n = 13), Both groups were comparable according to age, body mass index and severity of trauma (PTS-test: 38.8 +/- 12.5, PTS-control: 40.8 +/- 15.5, ISS-test: 39.6 +/- 11.4, ISS control: 40.5 +/- 9.2). Patients were randomized to receive either Impact (test) or an isonitrogenous isocaloric diet (control). Feeding was started on the 2nd day after trauma via endoscopically placed nasoduodenal or -jejunal feeding tubes. The experimental diet was safe and well tolerated. During the 1st week the enteral feeding amount was about 2000 ml without significant difference. Test-fed patients developed SIRS significantly less frequently between day 1 and day 28 (8 vs 13.3; P < 0.05) and especially between day 8 and day 14 (3 vs 6.2; P < 0.001). In the control group the Goris score was significantly worse (P < 0.05) on days 3, 4, 6, 7, 10, 11, 16 and 17 and the Sauaia score on days 8, 9, 10 and 11 (P < 0.05; P < 0.01). Mortality rate did not significantly differ (test 2/16, control 4/13), nor did length of ICU or hospital stay. With regard to the acute-phase response, C-reactive protein was significantly lower on day 4 in the test group (test: 131 +/- 67 mg/l, control: 221 +/- 110 mg/l) as was fibrinogen on day 12 (6.6 +/- 1.4 vs 7.5 +/-i 1,4 g/l) and day 14 (7.1 +/- 1.3 vs 7.8 +/- 0,8 g/l). No significant difference could be observed for CD4/CD8 ratio, CD45 isotope on activated T-cells and lymphocytic interleukin (Il)-2-receptor- and Il-6 level. However, HLA-DR antigen presentation on peripheral monocytes was significantly elevated on day 7 in the test group (P < 0.05). According to the results, arginine, omega-3 fatty acids and nucleotides-enriched diet during early enteral feeding leads to reduction of SIRS after severe multiple injury. There is evidence for improvement of post-traumatic immunological response which helps to overcome the immunological depression after trauma.