Aleutian mink disease parvovirus (ADV) infects macrophages but infection is restricted. Using the human macrophage cell line U937, we reported infection to be antibody-dependent [22,23]. Recently, we learned that the U937 cells were contaminated with the human cell line, K562 [12]. To clarify which cell line actually supported ADV infection, we studied the antibody-dependent enhancement (ADE) of ADV infection in pure lines of U937 and K562. After infection with ADV complexed with mink anti-ADV antibody, up to 10% of the K562 cells, but none of the U937 cells showed evidence of infection. These results indicated that K562 cells, but not U937 cells, were susceptible to ADV. ADV-infected cultures of K562 were sorted by flow cytometry after staining with a murine monoclonal antibody (IV.3) directed against Fc(gamma)RII. Only cells that were IV.3 positive supported ADV gene expression. Also, preincubation of K562 cells with IV.3 blocked ADV infection by more than 90%. These results established that the ADE of ADV in K562 is Fc(gamma)RIIA-mediated.