OBJECTIVES: The etiology of pleural effusions (PEs) varies, and a percentage of PEs remains unexplained despite an intensive workup. One previous study documented a high prevalence of Epstein-Barr virus (EBV)-DNA in unselected and unexplained PEs. Our aim is to characterize the clinical and cytomorphologic features of EBV-associated PEs, which have not been described. METHODS: A database search was performed for PEs with EBV-DNA identified in the fluid by real-time quantitative polymerase chain reaction. The corresponding fluid cytology and chemistry were reviewed, and the patients' demographic data and clinical features were recorded. RESULTS: A total of 20 cases of EBV-DNA-positive PE were found. All patients had a history of lung transplantation. Most of the PE EBV loads were relatively low. Cytologically, polymorphous lymphocytosis was present in more than 70% of PEs. Scattered lymphocytic mitosis and apoptosis were seen in some cases. Mesothelial cells varied in number, and some cases showed reactive atypia. The lymphocytes were predominantly T cells with the CD4/CD8 ratio varying from 10:1 to 3:20. CONCLUSIONS: EBV infection/reactivation can account for certain proportions of "idiopathic" PEs. Polymorphous lymphocytosis is the most common cytologic feature, but atypical features (in both lymphocytes and mesothelial cells) can be seen.