The zebrafish has become an important new animal model for drug screening, target identification, and validation of various disease models. Although progress has been made in adapting image based high- content screening systems, there are several challenges for automation. To date, the quantitative evaluation of zebrafish assays is performed semi-manually at best, which constitutes a significant bottleneck in terms of workflow and screening cost. In Phase I research, we will specialize software algorithms that will enable automated quantitative assessment of various toxicity endpoints, thus allowing the screening of a large number of potentially toxic compounds. PUBLIC HEALTH RELEVANCE: Use of zebrafish as an alternative animal model for drug screening can greatly accelerate the drug screening process, decrease costs, and provide more accurate results than cell-based assays.