ObjectivesThe purpose of this study was to determine whether apoptosis is a major mechanism of cell death in patients with sepsis. The activities of caspase-3 and the antiapoptotic protein, BCL-2, were investigated also.DesignA prospective study of 20 patients who died of sepsis and multiple organ dysfunction was performed. The control group of 16 patients consisted of critically ill, nonseptic patients who were evaluated either prospectively[7]or retrospectively[9]. In addition, normal colon sections from seven patients who had bowel resections were included. Apoptosis was evaluated in hematoxylin and eosin-stained specimens by deoxyuridine triphosphate nick end-labeling (TUNEL) and by DNA gel electrophoresis.SettingTwo academic medical centers.PatientsCritically ill patients.Measurements and Main Results25% to 50% of cells being positive focally in the splenic white pulp of six septic but in no nonseptic patients.ConclusionsWe conclude that caspase-3-mediated apoptosis causes extensive lymphocyte apoptosis in sepsis and may contribute to the impaired immune response that characterizes the disorder. (Crit Care Med 1999; 27:1230-1251)