To assess factors that may influence the immunogenicity of oral poliovirus vaccine (OPV), neutralizing antibody responses were measured in 1409 infants in Brazil and the Gambia who were randomized to receive one of four different formulations of OPV at approximately birth and at 6, 10, and 14 weeks. Overall seroconversion rates at the end of the trial were 85% for poliovirus type 1 (P1), 94% for type 2 (P2), and 68% for type 3 (P3). Factors associated with vaccine failure included high levels of maternal antibody (P1, P2, and P3), vaccination during the rainy season (P1, P2, and P3), diarrhea at the time of vaccination (P2 and P3), household exposure to other OPV recipients (P1), and breast-feeding (P3) (P < .05 for each factor, logistic regression analysis). OPV containing twice the standard potency of Sabin type 1 virus increased seroconversion rates to P1 by 8% in Brazil (P < .05) and 15% in the Gambia (P < .001). Suboptimal responses to OPV in developing countries are determined by a complex array of factors related to the vaccine, host, and environment.