During the clinical development of safe, well tolerated and immunogenic vaccines against hepatitis A the persistence of protective antibodies was estimated, based on relatively short observation periods of 18 months to 3 years. We report here on longterm persistence of antibodies in volunteers who participated in one of the early clinical trials on inactivated hepatitis A candidate vaccines. In a randomized trial three groups of altogether 110 healthy adults, initially hepatitis A virus (HAV) seronegative persons were vaccinated with an inactivated hepatitis A vaccine according to the schedule 0-1-2-12 months. One group received 180 ELISA units, one group 360, and one 720 ELISA units per dose. Blood samples were taken prior to the first vaccination and at months 1, 2, 3, 4, 6, 12, 13, 18, 24, 36 and 84. The decrease of antibodies was characterized by two disappearance rates: a rapidly decreasing component and a slower decreasing one becoming predominant ca 12 months after booster vaccination. The disappearance of antibodies could be described by a two-component model which holds for t > or = 13 months. The estimated disappearance rates for the slow component (annual decrease) was found to be 11 and 13% for the 180 and 360 El. U groups, respectively (the 720 El. U group showed no decline, which was probably due to the small sample size). The estimated persistence of antibodies within protective range varied between 24 and 47 years depending on individual titres reached at month 13 and vaccination dose.