Objective: To investigate the deformability of morphologically active and passive neutrophils in patients with sepsis (SP), septic shock (SS), and adult respiratory distress syndrome (ARDS), Design: Prospective, observational study. Setting: A university hospital intensive care unit and research laboratory. Patients: Six patients with sepsis, six patients with septic shock, and six patients with ARDS. Eight healthy volunteers and eight ventilated but noninfected patients served as controls. Interventions None. Measurements and Main Results: Morphologically passive and active neutrophil deformability as defined by the micropipette method was significantly decreased in patients with SP, SS, and ARDS associated with sepsis as compared with both control groups, Neutrophils from SS and ARDS patients were significantly more rigid as compared with neutrophils from SP patients but they did not differ from each other. The percentage of activated neutrophils was significantly higher in SP, SS, and ARDS patients. Increased passive neutrophil rigidity was significantly attenuated after coincubation with cytochalasin D. Tumor necrosis factor-a and interleukin-lp serum levels were significantly higher in SP, SS, and ARDS patients. Conclusions: The entire neutrophil population is less deformable in SP, SS, and ARDS patients. The decreased deformability of passive neutrophils suggests that a direct mechanism involving actin polymerization, distinct from cell activation, is involved. These observations may be important in the mechanism of impaired vascular flow in patients with sepsis.