Immediate-early genes are part of a cellular response mechanism that reacts to biochemical, electrical, pharmacological, and physiological stimuli as well as changes in behavioral state. In the brain, immediate-early genes-such as egr-1 have been used as markers for neuronal activity. These markers could be invaluable in studies that utilize the chick-quail chimaera system to investigate neural components of behavior. Therefore, we decided to clone avian homologs of immediate-early genes to allow an expression analysis in behavioral paradigms and to determine the degree of conservation among diverse species. We report in this study the cloning of the ZENK gene, an egr-1 homolog, from chicken, quail, zebrafinch, and canary. We show that the coding region of this gene is highly conserved and follows established phylogenetic relationships. In situ hybridization demonstrates that the expression pattern is also conserved among species. We further demonstrate that there are regions in the 3' untranslated area of the ZENK gene that are as highly conserved as the protein-coding region and that may play a role in postranscriptional regulatory mechanisms of ZENK gene expression.