To determine the predictive value of plasma interleukin (IL)-6 and tumor necrosis factor-alpha (TNF) measurements in assessing bacteremia and subsequent morbidity and mortality rates in emergency department patients. Prospective case series. Emergency department and inpatient services of a large urban university hospital. A total of 100 patients admitted through the emergency department with signs of infection and the presumptive diagnosis of bacteremia. Blood samples were collected for cytokine determinations. IL-6 and TNF concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in plasma samples obtained on patient admission to the emergency department. Patient's hospital course and culture results were documented by chart review. Severity of patient illness was estimated serially using the Acute Physiology and Chronic Health Evaluation (APACHE) II scoring system at entry into the study, and then again at 24 and 48 hrs. A quantified, subjective assessment of the severity of patient illness was recorded by the admitting physician in the emergency department. Multivariate logistic regression analysis using the variables of plasma IL-6 concentrations, TNF concentrations, APACHE II score at entry, physician assessment of illness severity, and patient age indicated that of these variables, only plasma IL-6 concentrations predicted bacteremia (p = .006) and death from infection (p = .009). A plasma IL-6 concentration > or = 2.0 ng/mL detected bacteremia with a positive predictive value of 72.7%, a sensitivity of 42.1%, and a specificity of 96.7%. Plasma TNF concentrations predicted mortality from all causes (p = .009) as did physician assessment of illness severity (p = .001). Increased APACHE II scores predicted the use of vasopressor medications (p = .002), length of hospital stay (p = .001), and subsequent increased APACHE II scores (p = .001) but did not predict bacteremia, death from infection, or death from all causes. Greater patient age predicted admission to the intensive care unit (p = .016). Measurement of plasma IL-6 concentrations in a population of emergency department patients with apparent bacterial infections predicted bacteremia and death from infection. The characteristics of the test indicated a potential use in selecting patients for the administration of novel therapies for sepsis.