Cytomegalovirus (CMV) is recognized as a common cause of infectious esophagitis in patients with the acquired immunodeficiency syndrome (AIDS). The radiographic and endoscopic findings are variable, and although some features are suggestive of CMV esophagitis, none is specific. The mainstay of the diagnosis of this disease has been histologic demonstration of the characteristic intranuclear and intracytoplasmic inclusions. We report three patients with AIDS-related CMV esophagitis in whom cytologic smears from esophageal brushings contained diagnostic cells characterized by nuclear and cytoplasmic enlargement; marginated chromatin; large, basophilic intranuclear inclusions surrounded by a clear halo; and granular, eosinophilic intracytoplasmic inclusions. In one case the initial diagnosis was made from the biopsies, and only after careful review were cells diagnostic of CMV infection identified in the cytologic smears. In that patient, numerous cells with herpes simplex virus-related changes were present and probably masked the presence of the CMV-infected cells. In contrast, the biopsies from another patient showed only necrotic debris and inflammatory cells, whereas the cytologic preparations revealed cells with the characteristic CMV inclusions. With improved therapy for this often-debilitating opportunistic infection, rapid and accurate diagnosis is imperative. Cytology complements histology, and concurrent use of these diagnostic modalities will detect CMV esophagitis more frequently than will either technique alone.