Salivary glands are an attractive target for gene transfer. Salivary epithelial cells are considered to be highly differentiated and have low rates of cell division (*6 months), affording the opportunity to obtain relatively long-term transgene expression in the absence of genomic integration. Here, we report a novel modified hybrid adenoretroviral vector, which provides stable transgene expression in salivary epithelial cells in vivo for up to 6 months in the absence of genomic integration. This modified hybrid vector, Ad DE1/3 LTR 2 EF1a-hEPO, encodes human erythropoietin (hEPO) and differs from a previously developed hybrid vector, AdLTR 2 EF1a-hEPO, by having more extensive E3 gene deletion. Following direct salivary gland gene transfer by retroductal cannulation, rats transduced with Ad DE1/3 LTR 2 EF1a-hEPO had sustained, elevated serum hEPO levels and hematocrits for 6 months (length of experiment), as compared with *2 months for animals administered the AdLTR 2 EF1 a-hEPO vector. Immunohistochemistry demonstrated that this novel vector could transduce both acinar and ductal cells. Interestingly, the Ad DE1/3 LTR 2 EF1a-hEPO vector evoked much weaker local (salivary gland) immune responses than seen after AdLTR 2 EF1a-hEPO vector delivery, which likely permits its significantly lengthened transgene expression in this tissue.