Polyhydroxycarboxylates (MW: 3,800-14,000) derived from phenolic (PDP) compounds have been found to inhibit the cytopathicity of HIV-1 and HIV-2 in MT-4 cells at concentrations that are not toxic to the host cells. The PDP compounds also inhibited syncytium formation in cocultures of MOLT-4 cells with HIV-1- or HIV-2-infected HUT-78 cells. They also interfered with the binding of OKT4A/leu3a monoclonal antibody (mAb) to the CD4 receptor, the binding of anti-gp120 mAb to HIV-1 gp120, and attachment of HIV-1 virions to MT-4 cells. The anti-HIV activity in this series of compounds can be ascribed to inhibition of the gp120-CD4 interaction and seems to depend on the presence of the anionic carboxylate groups. Their mechanism of action is similar to that of the heterogeneous polymer aurintricarboxylic acid (ATA).