Purpose. The NIH Molecular Libraries Roadmap Initiative wishes to encourage HTS assay applications from investigators who have the interest and capability to work with the Molecular Libraries Probe Production Centers Network (MLPCN) for chemical probe development. This Funding Opportunity Announcement (FOA) promotes discovery and development of new chemical probes as research tools for use by scientists in both the public and private sectors to advance the understanding of biological functions and disease mechanisms. This initiative is one of the integrated components of the NIH Molecular Libraries Roadmap initiative that offers biomedical researchers access to large-scale automated high throughput screening (HTS) centers in the MLPCN, diverse compound libraries in the Small Molecule Repository (MLSMR) and information on biological activities of small molecules in the PubChem BioAssay public database. Mechanism of Support. This FOA will utilize the NIH Small Research Grant (R03) grant mechanism. Funds Available and Anticipated Number of Awards. The total number of assays to be selected depends on the scientific merit of applications and the availability of resources within the MLPCN. The MLPCN intends to select and implement 100 HTS assays annually starting in 2008 to support novel and significant probe discovery and development.