As multiple-organ failure (MOF) has been generally associated with sepsis, the importance of bacterial sepsis was evaluated retrospectively in 55 trauma and 37 intra-abdominal-sepsis patients with MOF. The severity of MOF was graded, and an analysis was made of day of onset, incidence, severity, sequence, and mortality of organ failures. No difference was found between groups in sequence, severity, or mortality of organ failures. In contrast, bacterial sepsis was found in 65% of intra-abdominal-sepsis patients but only in 33% of trauma patients. It is concluded that sepsis is probably not the essential cause of MOF. Instead, an alternative hypothesis is presented involving massive activation of inflammatory mediators by severe tissue trauma or intra-abdominal sepsis, resulting in systemic damage to vascular endothelia, permeability edema, and impaired oxygen availability to the mitochondria despite adequate arterial oxygen transport.