B19 parvovirus is pathogenic in humans. The virus propagates in the bone marrow, where it is cytotoxic to erythroid progenitor cells. Antibodies appear in blood after infection and neutralize virus in vitro; infection appears to confer lasting immunity. The predominant immune response on immunoblot is to the minor capsid protein (VP1), which differs from the major capsid protein (VP2) by an additional 227 amino acids. We previously demonstrated that antisera directed to a fusion protein containing this unique region or to more limited fusion peptides of 50-100 amino acids each neutralized virus. In the current work, we tested synthetic peptides of about 20 amino acids derived from the VP1 unique region for their ability to elicit a neutralizing antibody response in rabbits. Individual peptides were covalently linked to a lysine core to produce a multivalent antigen. Animals produced antibodies to all 13 synthetic peptides, as determined by ELISA. At 12 weeks, animals injected with one of three peptides--two from the far amino terminus and the third from the center of the unique region--had produced antibodies that completely neutralized virus; by 16 weeks, antisera elicited with another four peptides also were effective. In summary, we identified regions containing neutralizing epitopes within the first 80 amino acids and amino acids 148-205 of the unique region. Our data suggest that synthetic peptides might be useful vaccine reagents for protection against parvovirus infection in humans.