A histologic review of 102 cases of Castleman's disease of the hyaline-vascular type, with a detailed paraffin immunophenotypic study of 23 of them, was undertaken to evaluate the morphologic variability of this disorder and its immuno/cyto-architectural characteristics. All cases had features in common including: abnormal follicles, with increased vascularity, poorly formed germinal centers and predominance of the mantle zone; lack of sinuses; and hypervascular interfollicular tissue containing large numbers of KP1-positive plasmacytoid monocytes. Networks of actin-positive cells [fibroblastic reticulum cells (RCs) or "myoid cells"] and KP1-positive dendritic cells (histiocytic RCs) were seen. There were differences in the proportion of follicles to interfollicular tissue, which covered a continuum from a "follicular", through a "classic", to a "stroma-rich" variant. The last-mentioned was qualitatively different as it showed loss of HECA-452 and MECA-79 reactivity in the blood vessels, decreased plasmacytoid monocytes and increased myoid cells and histiocytic RCs. In 5 cases there was formation of distinct nodular growths which varied from spindle cell foci to angio-histiocytic-RC proliferations, all of which may be confused with vascular or follicular dendritic RC neoplasms. From our findings, data from the literature and the working hypothesis that plasmacytoid monocytes are the precursors of both follicular dendritic RCs and sinus lining cells (Parwaresch et al.), a pathogenetic theory is proposed for this type of Castleman's disease which postulates that a developmental block in plasmacytoid monocytes results in their accumulation with poor formation of germinal centers and sinuses under stimulation. The lack of sinuses would lead to impaired egress of circulating lymphocytes which, however, would continue to enter the node through functional high endothelial venules and to accumulate in the mantle zone. The factors responsible for angiogenesis and for the cellular growths that characterize the stroma-rich variant remain to be determined, as do the relationships between the three variants.