The early diagnosis and effective treatment of cytomegalovirus (CMV) pneumonia remains a keystone for patient survival after lung transplantation. At present, the use of DHPG (ganciclovir sodium) opens the possibility of a potent antiviral therapy. The use of monoclonal antibodies directed to immediate early CMV antigens offers a fast method to detect the early phase of systemic or local viral replication. Five single lung and heart-lung transplant patients at high risk for CMV infection (donor, CMV-positive; recipient, CMV-negative) were monitored by cellular immunohistology for immediate early antigens. Specimens from bronchoalveolar lavage (n = 39) and bronchial biopsies (n = 17), and peripheral blood leukocytes (n = 57) were examined. In peripheral blood leukocytes and bronchial biopsy specimens no CMV-positive cells were detected. The bronchoalveolar lavage analysis of two patients showed immediate early antigen-positive cells after 1 to 3 months. At the same time the patients had clinical symptoms that could also be related to lung rejection. Serologic conversion (CMV-IgM) occurred only 6 days later in one patient with informative follow-up analysis; CMV culture (available 4 to 6 weeks later) confirmed the diagnosis retrospectively. DHPG treatment was started immediately and resulted in CMV antigen negativity in bronchoalveolar lavage fluid after one or two courses (10 mg/kg/day; 14 days). Direct antigen detection offers a fast and specific monitoring of early CMV infection. The implications to the clinical management of lung transplant patients are discussed.