The method we describe in this chapter describes the synthesis and use of cDNA macroarrays for determining changes in gene expression due to environmental toxicants as well as the methods and materials that are required to do this work. While the details are for investigators working with nontraditional species for which commercial arrays are unavailable, anyone can design and use their own custom arrays using these protocols. We have intentionally left out details for statistical analysis for the arrays as the methods for doing this are still being developed and would need to be specific to the experiment being done. In all, gene macroarrays are a relatively easy way to generate large amounts of data in a short amount of time.