Pneumonia continues to be a major cause of disease and death among patients worldwide. Aspects of the host response to infection, such as the release of cytokines, may be contributing to the persistent morbidity and mortality.Plasma levels of cytokines interleukin (IL)-1 beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) were measured in critically ill patients with pneumonia (ICUP; n = 12) and less severely ill patients with pneumonia (NONICUP; n = 8), and in 2 additional control groups of patients, viz, severely ill postoperative patients without evidence of infection (POSTOP; n = 11) and less severely ill patients with nonpneumonia infections (NONP; n = 9). All four groups of patients were studied in a multivariate one-way analysis of variance using the parameter vector: plasma IL-1 beta, IL-6, TNF-alpha, systolic blood pressure, diastolic blood pressure, plasma urea, creatinine, and temperature. Thereafter the significance of individual parameters were assessed by univariate analysis and pairwise comparisons.All cytokine concentrations were highest in the ICUP group. In the case of IL-1 beta, levels were significantly higher in the ICUP group when compared with the noninfected POSTOP group. The acute physiology and chronic health evaluation (APACHE) II scores were identical in these two groups (17 +/- 3 [SD] and 10 +/- 1, respectively, not significantly different). Intermediate levels were found in those groups with intermediate levels of infection. The IL-6 levels were not significantly different between the groups and in particular, the levels in the ICUP and POSTOP groups were similar. The TNF-alpha levels tended to mimic those of IL-1 beta, although the significant difference found was between the ICUP and NONICUP groups which had significantly different APACHE II scores (17 +/- 3 vs 4.4 +/- 1, respectively). No association between cytokine levels and patient mortality was demonstrated.Among the cytokines, IL-1 beta appeared to be associated with the severity of infection, IL-6 appears to reflect severity of stress whether of infection or noninfective origin, and TNF-alpha may be a marker of severity of pneumonia.