Although rates of seroconversion following administration of trivalent oral poliovirus vaccine (TOPV) approach 100% in industrialized countries, only 73% (range, 36%-99%) and 70% (range, 40%-99%) of children in developing countries have detectable antibody to poliovirus types 1 and 3, respectively, after three doses. While factors accounting for these differences have not been fully elucidated, available data suggest that type 2 vaccine virus and enteric pathogens often interfere with responses to types 1 and 3 vaccine viruses but that this interference may be overcome by modifying the absolute and relative dosage of the three Sabin types. Increasing the interval between doses beyond 30 days may also be important, in view of the prolonged excretion of vaccine virus and the potential for interference with responses to subsequent doses. Although advances in molecular biology may ultimately lead to the development of more-immunogenic vaccine candidates, approaches such as increasing the number of doses of TOPV, mass vaccination campaigns, and combined use of oral and inactivated vaccines should also be considered.