To determine the role of human metapneumovirus (HMPV) in respiratory tract infections (RTIs) of lung transplant recipients, 60 patients were prospectively enrolled in this study spanning from September 2005 to November 2007. Community-acquired respiratory viruses (CARVs) were identified by polymerase chain reaction and tissue culture in respiratory secretions. Of 112 RTIs, 51 were associated with > or =1 CARV, including 7 HMPV, 13 respiratory syncytial virus (RSV), 19 parainfluenza virus 1, 2, or 3 (PIV), 16 influenza A or B (FLU), and 3 human rhinoviruses (HRV). Sixteen CARV-RTIs had multiple pathogens. While the standard protocol was to admit all paramyxoviral RTIs for inhaled ribavirin, 16% CARV-RTIs required hospitalization because of the severity of their respiratory compromise, including 25% of HPMV-single-agent RTI, 38% of RSV single-agent RTI, 10% of PIV-single-agent RTI, and 19% of multiple-agent RTIs. None of those with non-CARV RTIs required hospitalization. The incidence of clinically diagnosed acute graft rejection in the first 2 months after an RTI varied from 0 for single-agent HRV to 88% for single-agent RSV (25% for single-agent HMPV). A new diagnosis of chronic graft rejection in the first year after an RTI was made in approximately 25% of the RTIs and did not significantly vary with the etiologic agent. No deaths occurred during this study. In conclusion, HMPV was associated with 6% of the RTIs in lung transplant recipients and its morbidity was similar to the average moribidity of CARVs.