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OBJECTIVE To determine the relationships between cytokine concentrations and alterations in leukocyte functional antigen expression in sepsis. DESIGN Prospective, cross-sectional study. SETTING Respiratory, coronary, and medical intensive care units in a university hospital. PATIENTS Forty subjects consisting of: a) patients with severe sepsis, b) patients with sepsis, c) critically ill nonseptic patients, and d) normal controls. INTERVENTIONS None. MEASUREMENTS Plasma concentrations of interleukin (IL)-1 beta, IL-6, IL-8, IL-10, interleukin-1 receptor antagonist (IL-1Ra), and tumor necrosis factor (TNF)-alpha were determined by enzyme-linked immunosorbent assay (ELISA). Peripheral blood monocyte HLA-DR and CD14 expression and neutrophil CD11b expression were determined by flow cytometry. Measurements were taken within 24 hrs of admission to the intensive care unit and/or clinical presentation. MAIN RESULTS Significantly increased plasma IL-6, IL-8, IL-10, and TNF-alpha concentrations were observed in the severe sepsis group compared to normal controls. Increases in IL-1Ra were not significant. Monocyte HLA-DR expression, significantly decreased in patients with severe sepsis, was correlated both with IL-6 (p < .005) and IL-8 concentrations (p < .001). Both of these cytokines had close correlations to Acute Physiology and Chronic Health Evaluation (APACHE) II scores which were also correlated with monocyte HLA-DR. Neutrophil CD11b, which was increased in all infected patients, was significantly correlated with the ratio between IL-1 and IL-1Ra concentrations (p < .001). The percent of CD14+ monocytes was lowest in patients with severe sepsis and showed a significant covariate effect from IL-8 concentrations (p < .001). CONCLUSION These findings suggest that the expression of specific functional molecules on peripheral blood leukocytes is variably related to the net production of certain monokines in sepsis.