Sarcoidosis is an inflammatory disorder of unknown origin. The nuclear regulatory factor-kappaB (NF-kappaB) appears to play a key role in immune and inflammatory processes such as asthma, rheumatoid arthritis and inflammatory bowel disease. We hypothesized that NF-kappaB activation might be involved in the pathological process of sarcoidosis.Twelve sarcoidosis patients, biopsy proven, and five healthy control subjects, all nonsmokers, were studied. Blood samples were taken and routinely analysed for several parameters including the serum angiotensin converting enzyme (sACE) level. Mononuclear cells were isolated from these patients in order to quantify the NF-kappaB contents in the nuclear extract of the mononuclear cells.Mononuclear cells NF-kappaB expressed per mg protein were twice as high in both untreated (n = 5) and treated (n = 7) patients with sarcoidosis compared to the control subjects (p < 0.001). In contrast, the sACE level appeared to be low in the treated patients compared to the untreated patients (p < 0.01).These results indicate that the inflammation in sarcoidosis is associated with NF-kappaB activation. Moreover, the suppression of the activated NF-kappaB response by glucocorticoids seems less successful than the suppression of the sACE activity. Future studies should focus on the clinical relevance of this observation and establish the possible therapeutic consequences of the increased NF-kappaB activation in sarcoidosis.