While oral ganciclovir (OGCV) has been used as primary prophylaxis in patients at high risk for cytomegalovirus (CMV) infection after solid organ transplantation, its value in secondary prophylaxis is unknown. We have examined the use of OGCV as maintenance therapy following confirmed CMV infection on 16 occasions in 15 patients, in kidney (n = 4), kidney-pancreas (n = 3) lung (n = 6) and heart-lung (n = 1) recipients. OGCV was used in two distinct clinical situations. One group (n = 7) received OGCV as consolidation therapy (mean duration of 21 +/- 5 d) following i.v. ganciclovir induction therapy (mean duration of 16 +/- 5 d) for acute CMV infection, and sustained remission was achieved in 6/7 patients for a median follow-up of 300 d. In the second scenario, OGCV suppressed clinical disease in all patients with relapsing CMV infection (n = 9), with minimal or absent toxicity with a median follow-up of 152 d. OGCV reduced morbidity by allowing removal of central lines used for long-term i.v. therapy in patients with poor peripheral access. Hence, this study demonstrates the safe and effective use of OGCV as consolidation therapy after standard induction treatment with i.v. ganciclovir, and as long-term suppressive therapy in transplant recipients with recurrent CMV infection.