Anticancer compounds with greater chemical diversity will be available from screening producing organisms with greater biological diversity. Many fungi have been successfully investigated as sources of potentially useful natural products, but endophytic fungi and fungi that have close associations with insects have not been investigated in such a fashion. There is increasing evidence that such fungi will produce chemically novel and therapeutically useful natural products. In addition many endophytic and specialized fungi are species specific, and investigating fungi associated with indigenous, geographically restricted, and/or endangered species should maximize the probability of finding producers of novel secondary metabolites. Specific aims include: 1. Collection of 400 isolates annually of fungi that are specialized to live in close association with plants or insects. These include endophytic fungi and fungal symbionts of insects. Samples will be collected from a taxonomically diverse spectrum of plants and insects, with particular emphasis on endemic species from subtropical habitats. 2. Isolation and fermentation of pure fungal cultures. Fungi will be subcultured to produce pure strains and fermented to produce extracts for CODS. 3. Perform bioassay guided isolation of active constituents from the CODS-active extracts and provide pure compounds for further biological evaluation. 4. To structurally characterize the active compounds using spectroscopic and crystallographic techniques.