We assessed the value of the cytomegalovirus (CMV) antigenemia assay for diagnosing primary CMV infection in adults. The CMV antigenemia assay was performed for 40 patients admitted to our unit over a 2-year period with unexplained fever and suspected primary CMV infection. Nine of the 10 patients with primary CMV infection had positive CMV antigenemia assays, and the results were available within 5 hours. All 10 patients had a mononucleosis-like syndrome. All but one of the 30 other patients had negative CMV antigenemia assays. A false-positive result was obtained for a patient with systemic lupus erythematosus. Overall, the CMV antigenemia assay was 90% sensitive and 96% specific for the diagnosis of primary CMV infection. Therefore, the CMV antigenemia assay appears to be a simple, rapid, inexpensive test for the diagnosis of primary CMV infection in hospitalized adults.