The pathogenic human parvovirus B19 replicates only in erythroid progenitor cells. This virus was shown to bind to blood-group P antigen, as measured by hemagglutination. Erythrocytes lacking P antigen were not agglutinated with B19. Purified P antigen (globoside) blocked the binding of the virus to erythroid cells and the infectivity of the virus in a hematopoietic colony assay. Target cells were protected from infection by preincubation with monoclonal antibody to globoside. Knowledge of a parvovirus receptor has implications for understanding the pathogenesis of parvovirus infections and for the use of parvoviruses in gene therapy.