A randomized, double-blind, dose-escalation study evaluated the safety and efficacy of hepatitis C virus (HCV)-Ab XTL 68, a neutralizing, high-affinity, fully human, anti-E2 monoclonal antibody, in 24 HCV-positive patients undergoing liver transplantation. HCV-Ab XTL 68 or placebo was administered at doses from 20-240 mg as 2-4 infusions during the first 24 hours after transplantation, followed by daily infusions for 6 days, weekly infusions for 3 weeks, and either 2 or 4 weekly infusions for 8 weeks. Serum concentrations of total anti-E2 obtained during daily infusions of 120-240 mg HCV-Ab XTL 68 were 50-200 g/mL above concentrations in the placebo group. Median serum concentration of HCV RNA dropped below baseline in all groups immediately after transplantation. On day 2, median change from baseline in HCV RNA was ฯช1.8 and ฯช2.4 log in the 120-mg and 240-mg groups, respectively, compared with ฯช1.5 log with placebo. The difference was lost after day 7 when the dosing frequency was reduced. The coincidence of increases in anti-E2 with decreases in HCV RNA concentration indicate that the dose-related changes in HCV RNA concentration were a result of HCV-Ab XTL 68 administration in the 120-and 240-mg groups. The overall incidence of nonfatal serious adverse events was higher with placebo (60%) vs. all active treatments combined (42%). In conclusion, HCV-Ab XTL 68 may decrease serum concentrations of HCV RNA in patients after liver transplantation. Studies evaluating more frequent daily dosing at doses ฯพ120 mg are necessary to investigate sustained viral suppression in this population.