Fiscal Year 2004 (FY04) was a year of transition for the Office of Research and Development (ORD) Computational Toxicology (CompTox) Program. In previous years, a small number of proof-of-concept studies based on endocrine-disrupting modes of action were initiated; and general framework for a larger program was established. The framework laid out three general objectives for the program: (1) improving the linkages in the source-outcome paradigm; (2) providing tools for screening and prioritization of chemicals under regulatory review; and (3) enhancing quantitative risk assessment. The CompTox Program is now moving from primarily from a planning phase to an implementation phase. In FY04 the endocrine disruptor proof-of-concept projects advanced through completion of the development of an estrogen reporter cell line to complement the androgen receptor cell line developed previously, refinement of QSAR models for receptor binding, and development of an in vitro cell based assay for steroidogenesis. Three cell-based assays are scheduled for scale-up production against a larger set of chemicals in FY05. Ten existing intramural research projects received funding to apply genomic, metabonomic, or computational tools in an effort to quickly expand the program beyond the endocrine-disruptor domain.