This study evaluated the immunogenicity and safety/tolerability profile of an investigational formalin-inactivated hepatitis A virus vaccine (VAQTA; Merck Research Laboratories) in 150 seronegative healthy children, 4 to 12 years old. The vaccine was derived from virus grown in infected MRC-5 cells in either roller bottles or Nunc cell factories (Nunc, Denmark). Subjects were vaccinated intramuscularly in a two dose regimen initially and at 24 weeks: Group A (n = 50) with a 12-unit dose from a roller bottle lot; Group B (n = 50) with a 25-unit dose from another roller bottle lot; and Group C (n = 50) with a 25-unit dose from a Nunc cell lot. Sera for anti-hepatitis A virus antibodies were drawn 3 weeks before vaccination and 4, 24 and 28 weeks after the first dose. Seroconversion from < 10 mIU/ml to > or = 10 mIU/ml by modified HAVAB (Abbott Laboratories) was observed in 99% of subjects at week 4 and persisted in 100% of subjects at week 28 (4 weeks after the second dose). The ranges of geometric mean titers of anti-HAV for all subjects at weeks 4, 24 and 28 were 31 to 49, 51 to 79 and 7059 to 29,609 mIU/ml, respectively. The 12- and 25-unit dose levels of roller bottle yielded similar geometric mean titers. The rise in geometric mean titers after the booster dose was > 120-fold and was highest in the recipients of the 25-unit Nunc cell lot (P < 0.05 for Group C vs. B).(ABSTRACT TRUNCATED AT 250 WORDS)