To investigate the possible role of endogenous cytokines in the immunopathogenesis of sarcoidosis, a study of cytokines in lymph nodes obtained from patients with active pulmonary sarcoidosis was carried out using immunoperoxidase staining and radioimmunoassays (RIA). Cells stained for interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), which appeared to be CD3+ cells and CD14+ cells, respectively, were seen scattered around granulomas. In contrast, cells positive for interleukin-1 beta (IL-1 beta) were located in CD11c+ cells within granulomas. Lymph nodes of patients with sarcoidosis contained significantly higher amounts of IFN-gamma, TNF-alpha and IL-1 beta than control lymph nodes. The levels of IFN-gamma and TNF-alpha in extracts of lymph nodes were correlated with the histological status of the granulomas. IFN-gamma was detected in all stages, while the highest level of TNF-alpha was obtained from lymph nodes containing many active granulomas. The level of serum IFN-gamma was always lower than in lymph node extract and correlated significantly with either serum angiotensin-converting enzyme or serum lysozyme. Patients with positive gallium-67 uptake or bilateral hilar lymphadenopathy had high levels of either serum IFN-gamma or lysozyme. These results suggest that quantitative analyses of IFN-gamma and TNF-alpha in sera and lymph nodes may serve to elucidate the pathophysiology of sarcoidosis.