Five cases of inflammatory pseudotumor (IPT) of the lymph node were investigated by means of light microscopy and immunohistochemistry to elucidate its cellular composition. The IPT is composed of a proliferation of spindle cells, inflammatory cells, and small vessels, forming high and poor cellular areas. Many spindle cells correspond to activated histiocytes as they coexpress vimentin and macrophage-associated markers; they are intermingled with vimentin-positive fibroblasts and variable numbers of vimentin- and actin-positive myofibroblasts. This mixed-cell proliferation invades and/or destroys medium- and large-sized vessels in all cases. This study indicates that the spindle cell proliferation, identified as histiocytic and fibroblastic in nature, represents the main component of the nodal IPT. We speculate that release of cytokines by the activated histiocytes may result in the development of the complex histopathologic aspects of this inflammatory process and, if inappropriate, may represent the underlying pathogenic mechanism.