In an effort to prevent cytomegalovirus (CMV) pneumonitis, seven consecutive CMV-serone- gative lung transplant recipients of organs from seropositive donors (D+/R‒) were given ganciclovir, 2.5-5 mg/kg intravenously twice daily for the first 10-21 days after transplantation, and commercial polyvalent immune globulin, 200-400 mg/kg every 7-14 days intravenously, for the first 2-3 weeks after transplantation. This regimen was followed by oral acyclovir. Six patients developed CMV viremia and all developed CMV pneumonitis. Viremia occurred later in these patients compared with D+/R‒patients who received alternative forms of CMV prophylaxis or CMV-seropositive recipients who received no specific prophylaxis (P =.023 and P =.021, respectively). There was no statistical difference in incidence or time to onset of CMV pneumonitis. When given as described, prophylactic ganciclovir and immune globulin followed by oral acyclovir may have delayed CMV viremia but did not prevent it or pneumonitis in high-risk lung transplant recipients.