A 51-year-old man developed fever, cough, and dyspnea 5 days after completing murine monoclonal anti-CD3 antibody (OKT3) treatment for acute cardiac allograft rejection. Samples of BAL fluid grew influenza A virus. Progressive pulmonary infiltrates, respiratory compromise, and hypoxia developed, and the patient ultimately required 5 days of mechanical ventilation. Treatment with amantadine hydrochloride and ribavirin was prescribed, and the patient was discharged after 19 days. Influenza A virus has not been an important pathogen in cardiac transplant recipients. However, this is the first reported case of influenza A pneumonitis complicating anti-T lymphocyte therapy for cardiac allograft rejection. In comparison with our patient, two previously reported cases of influenza A infection in cardiac transplant patients have been less severe. The virulence of our patient's, life-threatening infection appears to be secondary to impairment of T lymphocyte-mediated immunity by OKT3. The role of therapeutic and even prophylactic amantadine therapy in this clinical setting has yet to be determined.