Twenty-two patients had bone marrow aspirates for culture and marrow trephine biopsies for histologic examination during the evaluation of an illness eventually proved to be disseminated histoplasmosis. These procedures provided evidence of involvement of the bone marrow with Histoplasma capsulatum in 19 cases. Fungi were demonstrated in trephine biopsy sections in 15 of the patients, permitting a rapid specific diagnosis. Three patterns of bone marrow morphology were observed; each reflected a variation of macrophage proliferation. In two of the patterns, diffuse macrophage proliferation and loose aggregates of macrophages, typical 2 to 4 μm intracellular histoplasma organisms were numerous and obvious in hematoxylin and eosin-stained sections. However, in the most common pattern, epithelioid granulomas, organisms were seen only in silver methenamine-stained sections, were infrequent and were often relatively large (6 to 12 μm). There were four patients from whom H. capsulatum was cultured when organisms could not be demonstrated in either hematoxylin and eosin- or silver-stained sections. The patients with diffuse proliferation of macrophages in the marrow comprised a distinct clinical group associated with immunosuppression, a fulminant course and a fatal outcome despite therapy. Patients in the other two morphologic groups responded well to therapy even though the immune responses in many were also suppressed. Bone marrow examination is an excellent diagnostic procedure in disseminated histoplasmosis. Trephine biopsies permit a rapid diagnosis in most cases and may be of prognostic significance.