Dengue is often associated with neutropenia and thrombocytopenia, suggesting that cells of the bone marrow may be targets of dengue viral infections. In this study we infected long-term marrow cultures with dengue type-2 (DEN-2) virus and characterized the viral antigen-positive cells. Using immunofluorescence microscopy and immunohistochemical staining, we demonstrated two types of stromal cells that were positive for DEN-2 virus antigens. The first was a population of relatively small (approximately 25 µm) CD11b/CD18 (MAC-1)-positive cells. When stained with anti-DEN-2 polyclonal antibody, these cells showed viral antigen-positive inclusions and, when stained with anti-tubulin or anti-vimentin antibodies, they showed a diffuse pattern of fluorescence, consistent with mobile dendritic cells with phagocytic functions. The second population of DEN-2 antigen-positive cells comprised a smaller proportion of the total cells. It was made up of larger cells (> 100 µm) that had a well-formed cytoskeletal system as demonstrated by intense staining with anti-actin, anti-tubulin, and anti-vimentin antibodies. When stained with anti-DEN-2 antibody, these cells showed a more diffuse pattern of fluorescence in the perinuclear and Golgi regions, consistent with ongoing virus replication. These large, strongly adherent cells were positive for nerve growth factor receptor, consistent with their identification as adventitial reticular cells. The molecule that mediates the virus interaction with susceptible cells has not previously been identified. Using plasma membrane proteins isolated from K562 cells, virus-binding studies suggest that an approximately 100-kD membrane protein may be involved in the initial virus-cell interaction.