Deficiencies in bone marrow stromal cells, i.e. fibroblasts, macrophages, endothelial cells and adipocytes, are considered to play a pathophysiological role in HIV-associated haematopoietic failure. Long-term bone marrow cultures (LTBMC) enable the longitudinal investigation of haematopoietic progenitor cell and bone marrow stromal growth. Therefore, in this study, the haematopoietic colony growth of bone marrow from patients with severe HIV infection was compared to that from healthy controls in LTBMC. The total cumulated number of colony-forming units/granulocyte-macrophage (CFU-GM) was 6.7-fold higher (293.6% vs. 44.0%, p < 0.01), that of colony-forming units/granulocyte-erythrocyte-macrophage-megakaryocyte (CFU-GEMM) was 3.5-fold higher (28.7% vs 8.3%), and that of burst-forming units/erythrocyte (BFU-E) was 31.1-fold higher (68.4% vs 2.2%) than that from HIV-positive patients, respectively (colony number before LTBMC = 100%). In contrast, the cumulated cell number at the end of LTBMC from HIV-positive patients was not reduced (cell numbers in percent of initially seeded cells: HIV-positive 418.4%, HIV-negative 397.1%). The significantly reduced colony-forming capacity over a significantly shorter time span, without reduction in the absolute cell number, in LTBMC from patients with severe HIV-infection as compared to healthy controls, suggests that uncoupling between cell proliferation and differentiation is a pathophysiological mechanism in HIV-dependent haematopoietic failure.