Interleukin-7 (IL-7) is a pleiotropic cytokine acting mainly on cells of the hematolymphoid system. In vitro studies have shown enhanced proliferation of acute lymphoblastic leukemia cells in response to IL-7. On the other hand, tumor cell lines transfected with a functioning IL-7 gene and subsequently transplanted into mice resulted in a prominent inflammatory infiltrate and reduced tumorigeneicity. These data suggest an important role of this cytokine in the pathophysiology of lymphoid neoplasms. Because little is known about the in vivo expression of this cytokine in various neoplastic and nonneoplastic lesions of the lymphoid system, we examined frozen and paraffin-embedded tissue samples of normal, reactive, and malignant lymphoid lesions using in situ hybridization with a 35S-labeled RNA probe specific for IL-7. Tumor cells of nodular sclerosing and mixed cellularity type of Hodgkin's disease displayed IL-7-specific signals in 24 of 31 cases. Among reactive lesions, only thymic tissue showed labeling within both cortex and medulla (4 of 7 cases), whereas in tonsils clear-cut IL-7-specific signals could not be found. Tissues infiltrated by B-type chronic lymphocytic leukemia or T- or B-type lymphoblastic lymphoma showed cytokine-specific signals in only one case of lymphoblastic lymphoma in rare reactive cells. In conjunction with the finding of elevated levels of IL-7 in the serum of many patients with Hodgkin's disease, our data suggest an important role of this cytokine in the pathogenesis of Hodgkin's disease. The prominent reactive infiltrate observed in most cases of Hodgkin's disease could be a consequence of elevated local levels of this cytokine as similar infiltrates are also observed in tumors in mice resulting from injection of tumor cell lines transfected with a functioning IL-7 gene.