OBJECTIVE--This review of the systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) provides an overview of a common but complex problem found in critically ill patients. It emphasizes definitions, common clinical patterns, metabolic responses, and pathophysiological changes. A brief discussion of treatment concepts is also included. DATA SOURCES--Data for this review were gathered from peer-reviewed journals, review articles by experts in SIRS/MODS, and selections from reference volumes written on SIRS/MODS. STUDY SELECTION--Reference selections were chosen on the basis of quality of research. Peer-reviewed journals were given primary consideration. Those review articles cited were felt to be essential to any discussion of SIRS/MODS. DATA EXTRACTION--Where possible, randomized, controlled, prospective studies were reviewed and conclusions used in this overview of SIRS/MODS. CONCLUSION--Our ability to care for critically ill patients has led to a new problem, SIRS and eventually MODS, which may become progressive organ failure and death. Unfortunately, these conditions are extremely frequent and carry high mortality rates. Increased oxygen consumption demands highlight the physiological response. The typical metabolic responses are characterized by hyperglycemia and accelerated protein catabolism. Unrecognized perfusion deficits, an uncontrolled septic focus, a persistent source of inflammation, or injured tissue is commonly present with SIRS/MODS and should be corrected. Restoration of oxygen transport and metabolic support are also important components of treatment. The cause of SIRS/MODS is complex and not fully understood, but multiple mediators and stimulated macrophages likely are important components and areas where treatment may well be focused.