A prospective case-control study of Lassa fever was established in Sierra Leone to measure the frequency and case-fatality ratio of Lassa fever among febrile hospital admissions and to better delineate the clinical diagnosis and course of this disease. Lassa fever was responsible for 10%-16% of all adult medical admissions and for approximately 30% of adult deaths in the two hospitals studied. The case-fatality ratio for 441 hospitalized patients was 16.5%. We found the best predictor of Lassa fever to be the combination of fever, pharyngitis, retrosternal pain, and proteinuria (predictive value together, .81); of outcome, the best predictor was the combination of fever, sore throat, and vomiting (relative risk of death, 5.5). Complications included mucosal bleeding (17%), bilateral or unilateral eighth-nerve deafness (4%), and pleural (3%) or pericardial (2%) effusion. Lassa fever is endemic in this area and is a more-common cause of hospital admission and death than has previously been described; this disease must be considered when diagnosing febrile illness in West Africa.