The efficiency of retrovirus-mediated gene transfer to primary airway epithelial cells from rhesus monkeys was evaluated. We compared the use of murine amphotropic retrovirus vectors to the use of murine retrovirus vectors containing the envelope (Env) glycoproteins from gibbon ape leukemia virus (GALV). These vectors use distinct receptors to gain entry into host cells. We found that vectors with the GALV Env glycoproteins are up to 10-fold more efficient at transducing genes into primary monkey airway epithelial cells than vectors with the amphotropic Env glycoproteins. Under optimal conditions, up to about 80% of primary monkey airway epithelial cells could be transduced with the vector containing the GALV Env glycoproteins. In addition, we found that delivery of retrovirus vectors to the apical side of polarized airway epithelial cultures was significantly more efficient than delivery to the basal side. These results suggest the feasibility of luminal delivery of retrovirus vectors to the lung.