The nine HTS centers comprising the NIH Mol. Libraries Probe Production Centers Network (MLPCN), part of the NIH Roadmap Initiative, conduct high throughput screens on assays submitted to NIH from biologists around the globe. MLPCN′s goal is not drug discovery but generation of probe compounds useful for elucidating biol. pathways. Since 2005, NIH′s Mol. Libraries Small Mol. Repository (MLSMR) has built a collection of over 300,000 compounds to facilitate MLPCN′s objective. The MLSMR compound collection comprises subsets of known biol. active compounds, natural products, targeted libraries, and compounds from academicians, as well as a large diversity collection. How is the MLSMR collection different from one designed for drug discovery? What is NIH′s strategy for building the MLSMR collection, and how will the collection evolve?.