Liver transplantation (OLTx) is a procedure offered to individuals with advanced liver disease who are expected to live less than a year. Despite improvement in the care of transplant recipients, these patients are exposed to large volumes of blood and, as a result, are at risk to acquire hepatitis. Currently, the only vaccines available for the prevention of hepatitis are those that induce a response to HB(s)Ag. In this study, 144 patients awaiting OLTx and 15 controls were vaccinated three times, once a month, intramuscularly in the deltoid using the Merck Hepatovax plasma-derived vaccine. This schedule was continued regardless of whether or not OLTx occurred before the series was completed. For the 15 controls, the response rate was 93% and for individuals with end-stage liver disease, it ranged from 44 to 54% (P < 0.004). No difference in the percentage of those developing antibody was detected between groups based upon disease indication or whether the vaccination series was completed before or after OLTx. Of the following: WBC, lymphocytes (percent and number), CD3+ cells (percent and number), CD4+ cells (percent and number), CD8+ cells (percent and number), CD4+/CD8+ ratio, and B cells (percent and number), only the absolute WBC (P < 0.05) distinguished between those who did and did not develop antibody. These data suggest: (1) those with chronic liver disease respond less well to Hepatovax than do controls; (2) a rapid sequence of vaccinations is capable of producing antibody in normals and those with liver disease; (3) no difference is evident between those who completed their vaccination schedule before or after OLTx; and (4) among patients with chronic advanced liver disease, a higher total WBC is associated with an increased rate of seroconversion.