CMV infection is a major cause of morbidity and mortality following liver transplantation (LT). A prospective study of 218 LT recipients showed that 55% of patients developed CMV infection during the 1st year post-transplantation. Symptomatic CMV infection developed in 25% of all patients, being a major cause of death (21% of all deaths). Of 62 episodes of documented organ invasion, liver was the major site (38 episodes), followed by lung (20), gastrointestinal (4), and retina (4). The main patient group at risk (according to CMV serology of the recipient [(R)/donor(D)]) was the R-/D+: 77% of patients developed CMV infection, all of them with symptoms. The lowest group at risk was the R-/D-: 13% of patients developed CMV infection, half of whom developed symptoms. Time-dependent multivariate statistical analysis of risk factors indicated that the R-/D+ group was the main risk factor for CMV infection (P < .02) and symptomatic infection (P < .0001). To decrease the incidence and severity of CMV infection following LT, a randomized study is ongoing to evaluate the efficacy of ganciclovir (5 mg/kg/IV/q 12 hours for the first 14 days post-LT) followed by acyclovir (800 mg/po/qid for 14 weeks) GCV + ACV (group I), versus acyclovir (same dose for 16 weeks, starting immediately post-LT) ACV (group II). These treatment groups are compared to matched historical controls (C). Preliminary analysis of 83 LT recipients indicates that in group I the median date for the first evidence of CMV infection is delayed (82 days) as compared to group II and C (41 and 33 days, respectively) (P = .004).(ABSTRACT TRUNCATED AT 250 WORDS)