Rev is a key regulatory protein of HIV-1. Its function is to bind to viral transcripts and effect export from the nucleus of unspliced mRNA, thereby allowing the production of structural proteins. Based on its essential role in viral replication, Rev is a potential anti-HIV therapeutic target. In our previous work, the structure of Rev was solved for first time by binding it to an antibody fragment (Fab). The Fab stabilized Rev allowing the formation of protein crystals suitable for X-ray structural analysis. Furthermore, the Fab was shown to have anti-HIV activity by binding tightly to Rev and blocking its functional interactions. Regions of the Fab antibody in contact with Rev define the paratope (regions of Rev in contact with the Fab are known as the epitope). The paratope consists of six complementary determining region (CDR); three each from the antibody heavy and light chains. The CDRs are relatively short consisting of 6 to 14 amino acid residues. Analyses of the epitope-paratope interface from the X-ray structure predicted key contacts or binding hot spots among the CDR sequences. Peptides corresponded to the CDRs were cyclized (N- to C-terminal) to give them a structure approximating to their conformation in the intact antibody. Of the CDRs peptides tested, LCDR3 exhibited tight binding to Rev and analogous to the parent antibody was capable of depolymerizing a highly associated form of Rev (filaments) by specifically disrupting Rev protein-protein interactions. The LCDR3 peptide and related peptides selected for their binding to Rev are being modified for cellular uptake and their anti-HIV activities evaluated. Rev functions as a multiprotein protein complex which is formed in the nucleus by binding to RNA followed by Rev oligomerization: the Rev-RNA complex then associates with carrier proteins which mediate export to the cytoplasm. Rev oligomerization is required for biological activity and the structure of oligomeric protein was determined using a combination of structural methods as a first step in understanding assembly of the active complex. This work is now being followed up by structural studies of Rev associated with RNA and accessory proteins. Apart from fundamental information on the mechanism of viral replication, these studies may highlight points of vulnerability which may be suitable targets for therapeutic intervention. HIV protease, a homodimeric protein, is essential in the viral life cycle and a major anti-HIV drug target. We have expressed and purified a number of wild type and drug resistant forms of the protease which have been used in structural studies. Novel drugs which bind to the protease have been studied by co-crystallization and by examining the crystal structures used to rationalize and optimize drug binding. Structural details of interactions between drug moieties and protein have led to the synthesis of new compound with higher anti-HIV potency.