In experimental settings, the increased intestinal permeability (IP) following severe trauma is associated with increased serum concentrations of cytokines. Multiply injured patients are susceptible to the development of multiple organ failure (MOF). The aim of this study was to determine if altered IP after trauma was associated with upregulation of cytokines and if cytokines and IP influenced the development of MOF. In 30 multiply injured patients, IP was measured on days 2 and 4 after injury using the lactulose-mannitol (L-M) test, and the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-8 were determined simultaneously. The L-M ratio increased significantly from 0.049 (0.017-0.133) on day 2 to 0.150 (0.059-0.339) on day 4 (p < 0.02) On day 4, a significant correlation was also found between the L-M ratio and IL-6 (r = 0.43, p < 0.03). The IL-6 level on days 2 and 4 was significantly (p < 0.01 and p < 0.03, respectively) higher in MOF patients than in those without MOF, as was the TNF-alpha level on day 4 significantly higher (p < 0.04) in MOF patients. IP increases following multiple trauma, and on day 4 it correlates with the IL-6 level. However, in patients who develop MOF only cytokines are invariably increased, with IL-6 alone being significantly increased on both measurements in these patients.