Simpathica: A computational systems biology tool within the valis bioinformatics environment. This chapter describes the structure of the computational systems biology toolkit, Valis, in which Simpathica is embedded. The bioinformatics environment, Valis, includes tools for visualization of biological information, design, and simulation of in silico experiments, and storage and communication of biological information. The Simpathica system occupies a central role in our systems biology toolkit. It allows biologists to construct and simulate models of metabolic, regulatory, and signaling networks and then to analyze their behavior. The system then simulates the pathways thus entered. Coupled with a natural language system, the Simpathica tool allows a user to ask questions, in plain English, about the temporal evolution of the pathways previously entered. The Simpathica architecture consists of two main modules and several ancillary modules. A basic graphical user interface can be put together in a Valis form in a few hours, in that most of the widgets needed are standard controls of the form manager. There has been considerable interest in signaling pathways involving Wnt proteins, which form a family of highly conserved secreted signaling molecules. These proteins regulate cell-to-cell interactions during embryogenesis