- PURPOSE: To study the clinical and laboratory features of primary infection with the Epstein-Barr virus in adults who required hospitalization and to assess the difficulty in its diagnosis, the use of diagnostic procedures, and the associated costs of care. PATIENTS AND METHODS: We retrospectively identified all adult patients who were diagnosed with primary Epstein-Barr virus infection in our region between 1988 and 1997 using strict serologic criteria. The added costs of unnecessary diagnostic tests and treatment were estimated. RESULTS: The analysis included 47 patients (60% men) with a mean (±SD) age of 30 ± 14 years. The prime cause of admission was fever (83%). Compared with patients 35 years of age and older, those younger than 35 years were more likely to have pharyngitis (45% vs 10%) and lymphadenopathy (66% vs 17%). Younger patients also had a greater mean atypical lymphocyte count (17% ± 14% vs 8% ± 6%) and more abnormal hepatic enzyme levels. Inpatient work-ups resulted in 309 days of hospitalization, many diagnostic tests, and unnecessary empiric treatments (total 203 days of antibiotic therapy). Overall, unnecessary diagnostic procedures and medical treatments contributed an average of approximately $12,000 in health-care costs per patient. CONCLUSIONS: Testing for primary Epstein-Barr virus infection should be a routine step in the investigation of fever in adults of all ages. A higher index of suspicion might prevent unnecessary, sometimes hazardous inpatient work-ups from being performed, thereby reducing health-care expenses.