Coexistence of Hodgkin's disease and giant lymph node hyperplasia (Castleman's disease) is well documented in the literature. We present a unique case in which the original lymph node biopsy revealed interfollicular Hodgkin's disease (CD15+, CD30+, CD45-, Reed-Sternberg cells) with coexistent histologic features of the plasma-cell variant of Castleman's disease. The patient experienced a long-term remission following combined chemotherapy and radiation therapy. He presented at 18 years and again at 22 years later with clinical, hematologic, and histologic features of a multicentric plasma-cell variant of Castleman's disease without evidence of Hodgkin's disease. This unique case report further strengthens the association of Castleman's disease and Hodgkin's lymphoma. Two pathogenetic mechanisms for this association have been suggested: (1) secretion of interleukin-6 by Hodgkin's Reed-Sternberg cells and histiocytes, and (2) manifestation of an abnormal immune state associated with Hodgkin's disease. These two mechanisms may, indeed, be related.