Insects and other arthropods constitute over half of the living animal species on earth; they are important not only from a biological viewpoint, but as disease vectors, and as agricultural, forest, and household pests. Insects interact chemically with one another, with plants, with animal hosts, and with predators. This project is concerned with elucidating the chemistry of these interactions. For the arthropods themselves, attention will be paid not only to glandular substances, but also to systemic components that may play important roles in arthropod defense and/or communication. The venoms of spiders appear to be especially interesting, since some of their low molecular weight components cause paralysis of prey by novel mechanisms. An important objective will be the characterization and synthesis of some of these toxins from spider venoms. Another new objective will be the initiation of a synthetic program designed to define the structural requirements for the anti-viral activity recently described for the lucibufagins. Plants have been co-evolving with insects for many millions of years, and the chemical relationships between these two groups of organisms are rich and interesting. Our work with plants will emphasize the isolation and characterization of new insect repellents, and the utilization of plant alkaloids as insect defensive agents and pheromone precursors. In all cases, new compounds with demonstrable biological activities will be isolated and characterized. Chemical syntheses will be carried out to confirm structures and to provide material for bioassays. The overall objectives of this work are (1) to increase our understanding of natural regulatory mechanisms, (2) to provide the basis for new control techniques of disease vectors or other pests, and (3) to discover new chemistry which may be useful in the development of drugs for viral and neurological diseases.