The World Health Organization (WHO) asked the authors to create a comprehensive program for the development of vaccines against encapsulated bacteria as a guide for the WHO Programme on Vaccine Development. The goal is a new generation of safe, inexpensive, and easily administered vaccines that are immunogenic in infancy and provide prolonged immunity in the vaccinate, secondary immunization to community members not reached in the initial application, and/or herd immunity. The approach is to capitalize on advances in molecular biology, biochemistry, and immunology, and the agenda developed addresses the five genera that cause most morbidity in less-developed areas of the world: Neisseria, Streptococcus, Staphylococcus, Haemophilus, and Pseudomonas. Three strategic areas for study are emphasized: existing polysaccharide vaccines, natural immunity and pathogenesis, and evaluation of new or speculative alternative approaches. It is hoped that this agenda will stimulate the widest possible participation in this global initiative.