This project focuses on the bioassay-guided isolation and purification of naturally occurring anti-HIV or antitumor agents from aqueous and organic crude extracts which exhibit activity in one of the NCI's primary screens. Current investigations are focused upon HIV-inhibitory constituents of marine sponges in the genera Jaspis and Stelletta and anti-HIV agents from cultured cyanobacteria. These studies entail development of efficient isolation and purification protocols for the active materials. Subse- equently, spectrochemical characterization and complete structural identi- fication of the pure compounds are performed. Special emphasis is placed on the application of advanced, high-field NMR experiments for detailing structural elements of the active compounds. In addition, new methods are pursued for studying large peptides and small/medium molecular weight proteins which are active against HIV. Isolation and identification of structurally related metabolites which may provide appropriate compounds for structure-activity analyses are conducted, as required for detailed biological evaluation by appropriate LDDRD staff and other collaborators.