Adenosine deaminase (ADA), an enzyme of purine metabolism, is highly expressed in four tissues of the mouse: the maternal decidua, the fetal placenta, the keratinizing epithelium of the upper alimentary tract (tongue, esophagus, and forestomach), and the absorptive epithelium of the proximal small intestine. ADA is produced at relatively low levels in all other tissues. To identify genetic elements that direct appropriate prenatal and postnatal expression of the ADA gene, a segment of DNA including the ADA promoter and 6.4 kilobases of the adjacent 5' flanking region was tested for the ability to direct the expression of a reporter gene in transgenic mice. In seven lines of transgenic mice studied, this construct directed high levels of reporter gene expression in the placenta and forestomach and exhibited correct developmental regulation in these tissues. This construct failed to direct significant reporter gene expression to either the maternal decidua or the proximal small intestine. Thus, different gene regulatory elements are required to target high expression to the four tissues characterized by high levels of ADA.