The study of gene expression and regulation relies on the introduction of DNA into cells, which can be accomplished by a procedure called transfection. In vitro studies with transfected cells expressing the introduced genes (trans-genes) have provided many valuable insights into gene function. However, in vitro transfection methods cannot provide the complete range of responses possible in intact organs and tissues, which have unique anatomy and consist of different cell types. Thus, in vivo studies in whole animals remain a critical element in gene-function studies. The effective and efficient in vivo delivery of DNA into whole animals has presented significant challenges. Although much work continues to be carried out to improve the more commonly used viral and nonviral vectors for gene delivery, recent progress in the application of naked DNA methods (1-4, and the chapters in this volume) has offered valuable alternatives. The obvious utility of direct introduction of DNA into tissues without the requirement for a viral vector has stimulated development of several alternative delivery methods. Of these, the hydrodyamics method (5-8) offers a simple, convenient means for the expression of significant levels of transgenes in the organs, especially the liver, of mice.