• Although the conventional Bordetella pertussis vaccine, which consists of killed whole organisms, has been shown to be effective in preventing disease, it has been associated with transient local and systemic reactions and may produce encephalopathy, though rarely. A new acellular pertussis vaccine containing partially purified protein antigens, filamentous hemagglutinin, and lymphocytosis-promoting factor hemagglutinin has been developed for use in Japan. We compared the immunogenicity and reactogenicity of conventional and acellular pertussis vaccine. Forty children aged 4 to 6 years and 40 children aged 18 to 24 months, all previously immunized at appropriate times with conventional diphtheria and tetanus toxoids and pertussis vaccine, were enrolled. We randomly assigned children to receive either conventional pertussis vaccine or acellular pertussis vaccine in a double-blind fashion. The diphtheria and tetanus components in both preparations were identical. Equivalent rises in pertussis agglutinin titers and antibodies to filamentous hemagglutinin and lymphocytosis-promoting factor hemagglutinin were measured in both vaccine groups at both ages that we studied. However, reaction rates to the two vaccines in both age groups were strikingly different. Acellular pertussis vaccine was significantly less reactogenic for fever, pain, fretfulness, abnormal gait, and local reactions at the vaccine administration site. If studies in progressively younger children confirm its reduced reactogenicity and equal immunogenicity, and if large-scale trials indicate its efficacy, the acellular pertussis vaccine may be a more appropriate candidate than the current vaccine.