Tumor necrosis factor alpha (TNF-alpha) has been shown to play an important role in granulomatous diseases, including sarcoidosis. TNF-alpha starts affecting cell function by binding to specific, high-affinity receptors on the cell surface, and two types of TNF-alpha receptors have been identified. Recently, soluble forms derived these cell surface receptors (sTNF-R type I and type II) have been shown to exist and have been investigated in several diseases. The levels of sTNF-R type I and type II in serum from patients with sarcoidosis were measured, and the clinical significance of sTNF-R was evaluated. The levels of both sTNF-R type I and type II were significantly higher in serum from patients with sarcoidosis (n = 36) than in serum from control subjects (n = 15): type I, 1.93 +/- 1.28 ng/ml vs 1.31 +/- 0.40 ng/ml, p < 0.01; type II, 3.48 +/- 2.60 ng/ml vs 1.56 +/- 0.35 ng/ml, p < 0.001. The levels of these receptors were significantly higher in patients with active sarcoidosis than in those with inactive sarcoidosis: type I, 2.43 +/- 1.83 ng/ml vs 1.57 +/- 0.45 ng/ml, p < 0.05; type 4.71 +/- 2.24 ng/ml vs 2.25 +/- 0.77 ng/ml, p < 0.01. The levels of sTNF-R type I and type II correlated significantly with the level of ACE, r = 0.70, p < 0.01; and r = 0.55, p < 0.05, respectively. We conclude that measurement of the levels of both types of sTNF-R may be useful in the evaluation of disease activity in sarcoidosis.