Integration is an essential step in HIV replication and is catalyzed by an enzyme caged integmse. We have isolated equisetin (la), and a novel opposite stere&tetnical homolog, phomasetin (2a), from Fusariun~ he~emsporum and a Phomu sp. respectively. They inhibit the invitro recombinant integrase enzyme with ICm values of 7-20 pM. Unlike known inhibitors, these compounds also inhibit the integration reactions catalyzed by preintegmtion complexes isolated from HIV-l infected cells. 0 1998 Elsevier Science Ltd. All rights reserved.