Primary immunodeficiency diseases (PID) represent candidate genetic disorders for new therapeutic approaches. Our laboratory is developing gene therapy for patients with PID using autologous CD34+ hematopoietic stem cells (HSC). Gene therapy may circumvent problems with allogeneic HSC transplantation, especially graft rejection and graft-versus-host-disease. We are particularly interested in three PID: Dedicator of CytoKinesis-8 (DOCK8) deficiency, Leukocyte Adhesion Deficiency type 1 (LAD-1), and GATA2 Deficiency. For DOCK8 deficiency, and LAD-1, the disease gene has been cloned. The genetic basis for MonoMAC has now been determined to be due to mutations in GATA2.. Testing new vector constructs and transduction conditions for gene therapy would be considerably enhanced by the acquisition of peripheral blood CD34+ cells from patients with these immunodeficiency diseases.