Recent developments in gene transfer technology have expanded the range of in vivo experimentation and provided new insights that might be applicable to the treatment of human diseases. Somatic gene transfer may complement conventional transgenic animal experiments by allowing for more restricted gene expression. Salivary glands of rats are readily transduced in vivo by adenovirus vectors. This model has been used to demonstrate the effects of transferring a water channel (aquaporin) gene to glands that have been damaged by radiation. Submandibular glands that receive the aquaporin vector increase the stimulated salivary flow close to normal levels. The possible role of E2F1 in promoting cell regeneration in vivo was also explored. A vector expressing E2F1 was capable of increasing DNA synthesis in rat salivary glands, though complete mitosis was not observed. Future generations of vectors must overcome current limitations of efficiency, immunogenicity, and transient expression.