We studied lymph node fine-needle aspirations from 10 patients with primary Epstein-Barr virus (EBV) infections (infectious mononucleosis). There were five males and five females, aged 15-54 yr. The diagnoses were confirmed by blood morphology and heterophil antibody (HA) and EBV-specific serologic studies. Nine patients were HA-positive, nine were viral capsid antigen (VCA)-IgM-positive, and all 10 were VCA-IgG-positive and anti-EBV nuclear antigen (EBNA)-negative. Five patients were referred for fine-needle aspiration biopsies for clinically suspected malignant lymphoma (ML). Four of these patients had been tested for HA prior to fine-needle aspiration, with negative results in three cases. The heterophil-positive patient was referred for fine-needle aspiration due to very impressive unilateral cervical adenopathy. Cytologically, all cases showed atypia consisting of greater numbers of large immunoblastic lymphocytes than are usually seen in the reactive lymph node. Two cases were cytologically suspicious for malignant lymphoma but included a considerable background of polymorphic immunoblasts. We suggest that polymorphic immunoblastic proliferations in lymph node cytology are suggestive of infectious mononucleosis. Since several reactive and neoplastic processes mimic this pattern, cases not followed by both confirmatory serologic studies and resolution of adenopathy should be pursued by excisional lymph node biopsy.