A series of hexahydroxydiphenyl derivatives of ellagic acid have been synthesized as simple analogs of ellagitannins and evaluated for their inhibitory activity against HIV replication in H9 lymphocyte cells. Compound 10 was found to be a potent inhibitor of HIV replication in infected H9 lymphocytes with little cytotoxicity. In the course of our search for natural products as anti-HIV agents, we previously found that galloylquinic acids, especially tetragalloylquinic acids, were potent HIV inhibitors. Our further investigation of other classes of tannins revealed that punicalin (1), punicalagin (2) and punicacortein-C (3) are the most potent inhibitors of HIV replication. Since 1-3 all contain a gallagyl (tetraphenoyl) group, it suggests that this structure may be important for the HIV inhibition. In addition, the gallagyl group is considered to be formed biosynthetically from a hexahydroxydiphenoyl (HHDP) group and two galloyl groups. Therefore, the HHDP group is regarded as a basic skeleton for gallagyl group. Based on these observations, we have prepared derivatives of HHDP group from ellagic acid, and have evaluated their inhibitory effect on HIV replication.