Sepsis is a clinical syndrome characterized by fever, leukocytosis or leukopenia, tachycardia, increased cardiac index, reduced systemic vascular resistance, and hypercatabolism. It is generally believed to be a response to invasive infections, although an infectious source cannot always be identified in patients with sepsis. Over an 18-month period 287 patients were admitted for more than 48 hours to a noncardiac adult surgical intensive care unit. Data were collected concurrently and recorded in a computer database. Seventy-three patients (25%) developed sepsis, and 50 (68% of those with sepsis) had bacteremia, with a mean of 1.5 organisms and 3.5 positive blood cultures per patient. Only 22 of 50 patients with bacteremia had a potential infectious source, and there was a concordance of cultures from the putative source and the blood stream in only 10 patients. Forty-one patients with sepsis (56%) had no apparent infectious source, but 28 of these (68%) had bacteremia, often with multiple organisms. Forty of the 73 patients with sepsis died in the hospital. Mortality in sepsis could not be predicted by the presence of an infectious source (P > 0.35) and was not related to bacteremia (P > 0.75). Mortality was strongly associated with the development of multiple organ failure (P < 0.0001). Sepsis is a generic response to a number of physiologic insults and does not require infection for expression. This inflammatory response may have survival value by increasing oxygen delivery to sites of injury, but uncontrolled inflammation may cause dysfunction in several vital organ systems. The associated immunosuppression results in bacterial colonization of sites from which bacteria ordinarily are excluded.(ABSTRACT TRUNCATED AT 250 WORDS)