Patients with the acquired immunodeficiency syndrome uniformly exhibit hematologic abnormalities characterized by anemia and/or pancytopenia. In a study of 75 consecutive bone marrow biopsy specimens from patients with acquired immunodeficiency syndrome, 29% exhibited serous atrophy, characterized by marrow hypoplasia, fat atrophy, and deposition of extracellular "gelatinous" material (gelatinous transformation). The latter material was composed exclusively of glycosaminoglycans (alcian blue positive at pHs of 2.5 and 1.0, and sensitive to testicular hyaluronidase digestion). Excess glycosaminoglycan, which significantly alters the bone marrow microenvironment, is detrimental to erythropoiesis. The present findings support the concept that the damaged hematopoietic inductive microenvironment in patients with acquired immunodeficiency syndrome leads to failure of hematopoiesis, and, hence, to peripheral hematologic abnormalities.