Proinflammatory cytokines play an eminent role in pathophysiology of infection and inflammation. Their actual clinical importance is, however, uncertain. In this study, we tested the hypothesis that inflammatory cytokines could be useful in detection of infections in high-risk patients. We prospectively studied the diagnostic value of determination of concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and the 55- and 75-kd soluble TNF receptors (sTNFR-p55 and sTNFR-p75) in detection of nosocomial infections in 52 patients with acute ischemic stroke, as an exemplary high-risk group, and compared these findings to those of conventional inflammatory indicators of inflammation (C-reactive protein and leukocyte count). After 1 week of hospitalization, 27% of the patients had minor or moderately severe nosocomial infections. This subpopulation exhibited significantly increased concentrations of IL-6 and sTNFR-p55 but not of IL-1beta, TNF-alpha, or sTNFR-p75. As expected, levels of C-reactive protein and leukocytes were increased in infected patients. The sensitivity and specificity for detection of nosocomial infections at day 7 of hospitalization was highest for IL-6, followed by C-reactive protein and the leukocyte count. The data suggest that the proinflammatory cytokine IL-6, in addition to its considerable pathophysiologic importance in systemic inflammation, may be valuable in detection of infections in high-risk patients.