Computer-based three-dimensional (3D) reconstruction of histologic features permits the assessment of the spatial arrangement of complex structures and has the additional advantage of demonstrating aspects that may be obscured in conventional, two-dimensional evaluations. Until now the spatial appearance of histotopographic details in human bone marrow has not been investigated. In the present study we explored the use of 3D visualization techniques to determine the configuration of sinusoidal vessels and surrounding megakaryocytes in osteomyelofibrosis. Up to 34 serial sections were cut from each trephine biopsy block and stained sequentially by monoclonal antibodies against collagen type IV and megakaryocytes (CD61-Y2/51) to discriminate relevant structures selectively and with high contrast. Images were digitized, and contours were traced manually. A new fast and graphically interactive software package for the reconstruction of 3D objects employing a low-cost personal computer was developed. The system allows reconstructions from any serial image in solid model form using a fast triangulation algorithm. 3D reconstruction emphasizes the close spatial relationship between sinus walls and megakaryocytes in this disorder and exhibits enhanced vascularity with a complex 3D meshwork of branching and tortuous sinusoidal vessels. Furthermore, an increase in luminal distention and aberration from normal shape could be observed. Large and ameboid megakaryocytes were frequently found adjacent to the abluminal surface of the sinus. The method described permits more elaborate insight into the complex topographic relationship of these two morphologic features in human bone marrow and may stimulate applications to other interesting specimens that warrant 3D visualization.