Influenza virus infection may cause significant complications in liver transplant recipients, and whether vaccination is effective in these patients is controversial. We performed a study to assess the immune response to influenza vaccine in liver transplant recipients and patients with cirrhosis compared with healthy controls. Liver transplant recipients (n = 20), patients with compensated cirrhosis awaiting transplantation (n = 14), and healthy volunteers (n = 9) were administered the standard dose of the 1999 to 2000 inactivated trivalent vaccine (A/Bejing/262/95[H1N1]; A/Sidney/5/97[H3N2]; B/Yamanashi/166/98). Antibody responses to each component of the vaccine were measured at baseline and after 6 weeks by hemagglutination inhibition. Vaccination was well tolerated, and no major side effects were observed. A significant postvaccination increase in antibody titer to all 3 vaccine components was obtained in all groups. However, liver transplant recipients had significantly lower postvaccination geometric mean titers and geometric mean increases to the H3N2 component compared with patients with cirrhosis and controls. The rate of seroconversion to H3N2 after vaccination was also significantly lower in liver transplant recipients (15% v. 89%). We conclude that liver transplant recipients have a significantly impaired immune response to the influenza vaccine, and some patients may remain unprotected from influenza infection after vaccination. Further studies of modified protocols of influenza vaccination for these patients are recommended.