Prophylaxis with ganciclovir has decreased the initially high morbidity related to cytomegalovirus (CMV) after lung transplantation, but the optimal length of prophylaxis and the long-term outcome have not yet been established. The impact of CMV on the short- and long-term outcome was studied in 187 lung transplant recipients in Gothenburg, Sweden, 1990-2002. Among CMV-seronegative patients receiving grafts from seropositive donors (D+/R-), 88% developed CMV disease, 40% if both donor and recipient were CMV-seropositive (D+/R+) and 26% if only the recipient was CMV-seropositive (D-/R+). Among CMV-seropositive recipients (R+) on oral acyclovir prophylaxis, 38% developed CMV disease, as compared with 39% on intravenous ganciclovir for 4 weeks and 28% on oral ganciclovir for 14 weeks. On average, CMV disease appeared at 41 days in the R+ on acyclovir prophylaxis, at 75 days on 4 weeks of i.v. ganciclovir and at 162 days on 14 weeks of oral ganciclovir. CMV disease was associated with a statistically significant increased risk of developing chronic rejection (bronchiolitis obliterans syndrome) at both 1 and 2 y after transplantation. CMV disease also had a significant negative impact on survival, with a 10-y survival of only 32% as compared with 53% after asymptomatic CMV infection and 57% with no CMV.