To determine whether age and other readily obtainable clinical and laboratory variables could be used to predict illness severity in febrile adults, data were collected on 39 patients presenting to an emergency department (ED) with rectal temperature > or = 37.8 degrees C (100 degrees F). Serious illness was defined as (1) need for emergency surgery; (2) intubation; (3) hypotension requiring treatment; (4) bacteremia requiring antibiotics; or (5) death. Six variables were associated with serious illness in the univariate analysis. In a stepwise logistic regression model, only age (P < .0001) and leukocyte count (P < .002) were independently associated with serious illness. Optimal partitioning of these two variables showed that febrile adults younger than 50 years of age with leukocyte counts of less than 15 E9/L have a 5% incidence of serious illness (95% confidence interval [CI], 3% to 8%). In contrast, those who are > or = 50 years of age with leukocyte counts > or = 15 E9/L have a 36% incidence of serious illness (95% CI, 22% to 52%). Patients in this latter category should be carefully examined and considered for hospitalization before concluding that they may be safely discharged from the ED.