To examine the differences between primitive bone marrow (BM) and peripheral blood (PB) myeloblasts in acute myeloid leukaemia (AML), we compared CD34(+) myeloblasts of paired BM and PB samples from 14 AML patients in terms of surface phenotype, homing and engraftment in a xenogeneic transplantation model, and gene expression, based on microarray studies and quantitative polymerase chain reaction. While there was no significant difference in surface phenotypes between these two populations, in vivo assay showed significantly better homing potential of PB CD34(+) cells than BM CD34(+) cells. Significant correlation between homing and engraftment in AML samples was also noted. In addition, gene expression profiling of CD34(+) cells from five paired BM and PB leukaemic samples showed that genes involved in G-protein and prostaglandin signalling, chemotaxis and stress response, cell proliferation and apoptosis were down-regulated in PB CD34(+) myeloblasts. These data suggested that circulating primitive myeloblasts in AML are functionally different from those residing in the marrow compartment, and such differences may be partly regulated by the BM microenvironment.