Cryostat sections of 58 lymph nodes were immunostained with a polyclonal rabbit serum against IL-1 alpha, and with monoclonal antibodies directed to IL-1 alpha (Vmp18), IL-1 beta (Vhp20 and BRhC3), and tumor necrosis factor alpha (TNF alpha) (B154.7). Furthermore the presence of cytokine-containing cells was correlated with the expression of endothelial leukocyte adhesion molecule (ELAM-1; 29F2) and of human leukocyte antigen (HLA-DR) (OKIa-1) by endothelial cells. Cells containing IL-1 and/or TNF alpha were detected mainly in pathologic conditions characterized by reactive or neoplastic expansion of the lymph node paracortex. Cells positive for IL-1 were detected in 16 of 21 cases of Hodgkin's disease, in 4 of 4 cases of T-NHL, and in 5 cases of diffuse or mixed lymphadenitis. Interleukin-1 alpha was detected in macrophages, interdigitating reticulum cells (IDRCs), endothelial cells, and neoplastic Hodgkin's and Reed-Sternberg (H-RS) cells. Cells positive for IL-1 beta were much fewer and consisted mainly of macrophages. Hodgkin's Reed-Sternberg cells were negative for IL-1 beta even after in vitro stimulation with bacterial endotoxin. Tumor necrosis factor alpha (TNF alpha) was present in macrophages and H-RS cells. Endothelial leukocyte adhesion molecule-1 expression by endothelial venules was detected in 17 of 20 cases of Hodgkin's disease, in 2 of 4 cases of T-NHL, and in 5 of 5 cases of diffuse lymphadenitis. In these pathologic conditions, HLA-DR antigens also were expressed frequently by endothelial cells. Cytokine-containing cells and ELAM-1-positive high endothelial venules (HEV) were extremely rare in lymph nodes involved by follicular lymphadenitis (12 cases) or B-NHL (16 cases). In cases of reactive or neoplastic B-cell proliferations, HLA-DR-positive HEVs still were present often. Our results indicate that IL-1/TNF alpha production at tissue level is often associated with ELAM-1 expression by HEVs, but is less well correlated with expression of HLA-DR antigens by endothelial cells.