The total removal of craniopharyngiomas can be difficult because of their tendency to adhere to surrounding vital structures. Frequently, adjacent brain tissue is infiltrated by leukocytes and cytokine(s) produced by tumor cells may play a pivotal role in tissue reaction. To elucidate the molecular mechanism(s) underlying such local inflammation, we investigated the expression of interleukin (IL)-1alpha, interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha in 15 craniopharyngiomas using a combination of RT-PCR, immunoblots, and immunohistochemistry. Although RT-PCR detected the expression of IL-1alpha, IL-6, and TNF-alpha, immunoblots demonstrated remarkable protein expression only for IL-6. Immunohistochemical study found that the epithelial cell layer was strongly immunoreactive for IL-6. Tumor cell layers stained weakly or negatively for IL-1alpha and TNF-alpha. Sandwich ELISA showed that levels of IL-1alpha and TNF-alpha were significantly higher in the cyst fluid than in cerebrospinal fluid (CSF) but lower than 10-fold. As the concentration of IL-6 in cyst fluid was >50,000 times that in CSF, we suggest that IL-6 plays an important role in the inflammatory reaction that occurs in the interface between the craniopharyngioma and the brain parenchyma.