Zebrafish has been used for many years as a model to study development and disease. The ability of zebrafish to produce thousand of embryos in a synchronous manner has made zebrafish an invaluable tool for genetic and chemical screens. Since its emergence as an important model organism the molecular tools for studying zebrafish have been limited. In this chapter, we describe a simple method to identify DNA binding sites and chromatin architecture in erythrocytes from adult zebrafish using chromatin immunoprecipitation coupled with next generation sequencing. This technique has been used extensively and successfully in other systems and it will be a useful tool for studying epigenetics in zebrafish. Copyright © 2011 Elsevier Inc. All rights reserved.