The immune reaction in classical Hodgkin's lymphoma (HL) can be separated into an inflammatory response in the involved tissues and a generalized immune response in the patient. The local immune reaction in HL is by far the most prominent among all tumors, with the exception of so called T-cell-rich B-cell lymphoma, a subtype of large-cell B-cell lymphoma. The general immune response in patients with HL is best described as an acquired cellular immune deficiency, most likely a result of the presence of tumor, although some data in the literature suggest a preexisting immune deficiency. The cellular origin of Reed-Sternberg (RS) cells in classical and nodular lymphocyte-predominant HL is discussed elsewhere. RS cells and their mononuclear variants can be considered as clones of neoplastic B cells that, by secreting potent cytokines/chemokines, not only cause the symptoms of HL but also promote their own growth and evade immune surveillance. The characteristic histologic features of HL--the prominent inflammatory response, the influx of eosinophils, and the presence of fibrosis and sclerosis--may also result from the expression of a range of surface molecules and the production of cytokines and chemokines by RS cells.