Castleman's disease (CD) is a lymphoproliferative disorder characterized by enlarged hyperplastic lymph nodes. CD may be localized or multifocal, and is often associated with signs and symptoms of generalized inflammation. The systemic manifestations of CD have been previously attributed to an overproduction of interleukin-6 (IL-6) by the tumor, although there is evidence that IL-6 is not responsible for all of the symptoms. We describe a 9-year-old boy who developed Castleman's disease with systemic findings of hypochromic microcytic anemia, growth arrest, inflammation, and hyperimmunoglobulinemia. Following surgical resection, all of the symptoms and laboratory abnormalities resolved. Using reverse transcriptase polymerase chain reaction (RT-PCR) analysis of the tumor, we found elevated levels of IL-6 mRNA as expected, but also elevated levels of tumor necrosis factor beta (TNF-beta) and gamma interferon (gamma-IFN) mRNA. Because these cytokines are mediators of immune regulation and inflammation, we propose that TNF-beta and gamma-IFN also play an important role in the pathophysiology of Castleman's disease.