Binding experiments of 3H-labeled African swine fever virus to susceptible VERO cells have shown the presence of saturable binding sites for African swine fever virus on the plasma membrane. The Scatchard analysis of the binding data at equilibrium indicates the existence of about 10(4) cellular receptor sites per cell with a dissociation constant (Kd) of 70 pM. Virus entry into VERO cells is mediated by a saturable component, since tritiated African swine fever virus saturable binding and uptake were competed by the same amounts of unlabeled virus. Similarly, early viral protein synthesis and virus production were inhibited by concentrations of uv-inactivated virus that competed virus attachment to saturable binding sites, suggesting that specific receptors mediate the entry of African swine fever virus particles that initiate a productive infection in VERO cells. African swine fever virus binding to virus-resistant L cells was not mediated by saturable binding sites. As a result of the nonsaturable interaction the virus was not able to enter L cells and neither early viral protein synthesis nor viral DNA synthesis was detected, indicating that the absence of specific receptors for African swine fever virus is a factor that determines the resistance of L cells to the infection.