Patients with acute fever (less than three weeks' duration) and no localizing symptoms or physical findings to suggest a source (unexplained fever) may have self-limited illness or occult bacterial infection requiring prompt treatment. To develop a management strategy for patients with unexplained fever, we studied 880 adults who were evaluated for acute fever in an emergency room. At presentation, 135 (15%) patients had unexplained fever. Occult bacterial infection was found in 48 (35%) of these 135 patients, and 21 (44%) of 48 infected patients had bacteremia. Four bacteremic patients were incorrectly discharged from the emergency room without antimicrobial therapy. Neither a "toxic" appearance of the patient nor an initial temperature of greater than or equal to 39.4 degrees C (103 degrees F) were predictive of occult bacterial infection. An index of predictive features was developed that included: age 50 years or older; diabetes mellitus; a white blood cell count greater than or equal to 15,000/mm3 (15 X 10(9)/L); a neutrophil band cell count greater than or equal to 1500/mm3 (1.5 X 10(9)/L); and a Wintrobe erythrocyte sedimentation rate greater than or equal to 30 mm/h. In patients with 0, 1, 2, or 3 or more index features present, the proportions having occult bacterial infection were 5% (1/21), 33% (15/45), 39% (15/38), and 55% (17/31), respectively. All four bacteremic patients incorrectly discharged had two or more of the index features. Adults presenting with acute unexplained fever often have life-threatening bacterial infection. A simple clinical index can be used to estimate the likelihood of occult infection and may reduce the frequency of diagnostic error.