Technical Abstract: STUDY OBJECTIVES: Alterations in microvascular permeability are prevalent in patients with sepsis; a recent study reported that patients with septic shock had increased capillary filtration coefficient (Kf), a noninvasive index of microvascular permeability. We aimed to determine whether patients with severe sepsis had increased Kf, and whether the magnitude of Kf correlated with indexes of nitric oxide activity and neutrophil activation. DESIGN: Single-center, prospective study. SETTING: Twenty-five-bed ICU of a medical college-affiliated teaching hospital. PATIENTS: Fifteen ICU patients with severe sepsis based on the American College of Chest Physicians/Society of Critical Care Medicine consensus criteria of 1992, and 10 nonseptic ICU patients as control subjects. INTERVENTIONS: Kf was measured by venous congestion plethysmography, plasma nitrate/nitrite (NOx) by chemiluminescence, and neutrophil expression of alpha4-integrin (an index of neutrophil activation) by flow cytometry. MEASUREMENTS AND RESULTS: Septic patients had higher Kf than nonseptic control subjects. Kf of septic patients was 5.6 +/- 0.6 x 10(-3) mL.min(-1).100 mL tissue(-1).mm Hg(-1) (mean +/- SEM, mL.min(-1).100 mL tissue(-1).mm Hg(-1) = Kf units [KfU]) as compared to 3.9 +/- 0.5 x 10(-3) KfU in nonseptic ICU patients (p < 0.05). There was no correlation between plasma NOx and Kf, or between neutrophil alpha4-integrin expression and Kf in patients with sepsis. Septic patients with clinical evidence of edema had significantly higher Kf (p < 0.05) than nonedematous septic patients. CONCLUSIONS: ICU patients with severe sepsis have increased Kf, a noninvasive index of microvascular water permeability. The magnitude of hyperpermeability did not correlate with NOx levels or one index of neutrophil activation (alpha4-integrin expression). Presence of peripheral edema in these patients was associated with increased Kf, and may represent a simple, clinical indicator of altered microvascular permeability in sepsis.