Oral polio vaccine (OPV) is recommended for routine immunization in the United States in part because of its ability to induce intestinal and pharyngeal immunity to reinfection. Mucosal immunity produced by OPV and enhanced-potency inactivated polio vaccine (E-IPV) was compared by challenging vaccinees with type 1 OPV. Fewer OPV (25%) than E-IPV (63%) vaccinees excreted OPV virus in stool after challenge. The mean stool virus titer was higher and the duration of shedding longer among E-IPV excreters. Only one E-IPV and three OPV vaccinees shed virus in the pharynx after challenge. Prechallenge serum neutralizing antibody levels were not statistically different among E-IPV vaccinees who did and did not shed virus; these levels were much higher than those of OPV vaccinees. Poliovirus-specific IgA levels in stool did not correlate with viral excretion. E-IPV was less effective that OPV in preventing and limiting intestinal infection, even though it induced higher postvaccination serum antibody levels.