Efficient transduction of primary hematopoietic cell types by oncoretroviral vectors and lentiviral vectors with a variety of different envelope pseudotypes has proven to be difficult. We recently developed a lentiviral vector based upon a modified Sindbis virus envelope that allows targeted transduction via antibody recognition to specific cells in unfractionated cell populations. However, similar to other envelope pseudotypes, the utility of this vector for some primary hematopoietic cells was limited by low transduction efficiencies. Here, we report that transient treatment of cells with low pH culture medium immediately following infection results in marked enhancements in transduction efficiency for primary hematopoietic cells. In combination with antibody directed targeting, this simple technique expands the utility of targeting transduction to specific cells in mixed populations of primary cells.