Peripheral blood contains hematopoietic progenitors (PBHPs), which can be harvested in clinically relevant amounts by apheresis. PBHPs have been used as a source of progenitors alternative to marrow for autologous transplantation following intensive chemotherapy. We have determined culture conditions for growth and differentiation of PBHPs to the mature myeloid phenotype, which in the present study are employed to demonstrate the functional correction of an inherited disorder of myeloid cells in retrovirus-transduced human primary hematopoietic progenitors. Patients with chronic granulomatous disease (CGD) suffer from recurrent life-threatening infections because blood phagocytes fail to produce microbicidal superoxide (O2-.). One-third of the cases of CGD result from defects in the gene encoding p47phox, a cytoplasmic oxidase component required for O2-. generation. In the present study, a replication-defective retrovirus encoding p47phox was used to transduce PBHPs from patients with p47phox-deficient CGD, which resulted in significant correction of O2-. generation when PBHPs were differentiated to mature neutrophils and monocytes. This study provides a model for use of PBHPs in development of gene therapy for diseases affecting bone marrow.