Immunocytochemistry on three primary cultures of RCC tumor cells and immunohistochemistry on five frozen sections of RCC were performed by utilizing a monoclonal antibody (M-57) to human IL-4R. We found that all three RCC tumor cell cytospin preparations stained with anti-IL-4R monoclonal antibody. Tumor cells stained with IgG control did not show any staining. Similarly, five histologically proven RCC frozen sections prepared from nephrectomy specimens had moderate to intense immunoreactivity to IL-4 receptor antibody. RCC sections stained with normal mouse IgG2b showed only background type staining. Frozen section prepared from uninvolved kidney showed only nonspecific staining. A flow cytometric analysis of primary cultures of RCC tumor cells confirmed the immunohistochemical data and showed that almost all of the cells were positive for IL-4 receptor expression. These results demonstrate that human RCC express immunoreactive IL-4 receptors, which may be a target for diagnosis and therapy by an anti-IL-4 receptor antibody fused to toxins or radionuclides or alternatively by IL-4 toxins.