Morphological data obtained by electron microscopy have shown that African swine fever virus adapted to VERO cells enters swine macrophages, its natural host cell, by a mechanism of receptor-mediated endocytosis. Binding studies with 3H-labeled virus and competition experiments with UV-inactivated virus have shown that the virus entry that leads to a productive infection in swine macrophages is mediated by saturable binding sites on the plasma membrane. The virus also penetrated into rabbit macrophages that do not produce infectious virus and initiated the synthesis of some early viral proteins; however, the viral replication cycle was aborted since viral DNA synthesis did not occur. The interaction of ASF virus particles with rabbit macrophages was mediated by nonsaturable binding sites, suggesting that the lack of specific receptors in these cells may be related to the absence of a productive infection. A similar abortive infection was detected in macrophages from other virus-resistant animal species.