This study investigated the relationship between the clinical features of sarcoidosis and the level of peripheral blood gamma-delta (gamma delta) T cells. Both the mean percentage of T cells and the mean cell number of gamma delta T cells in the peripheral blood were significantly higher in patients with clinically active sarcoidosis than in patients with inactive sarcoidosis or active tuberculosis and in normal subjects (active sarcoidosis: 18.9 +/- 17.2%, 142 +/- 130.4 cells/microliters, n = 29; inactive sarcoidosis: 7.0 +/- 3.7%, 48.7 +/- 35.0 cells/microliters, n = 16; active tuberculosis: 4.3 +/- 3.2%, 47.9 +/- 36.6 cells/microliters, n = 19; control subjects: 5.0 +/- 1.9%, 77.6 +/- 37.7 cells/microliters, n = 12). gamma delta T cells were significantly elevated in patients with sarcoidosis for 2 yr or more or those with Stage III radiographs. The level of gamma delta T cells, however, showed no correlation to the serum angiotensin-converting enzyme, a marker of active granuloma formation. gamma delta T cells were scarcely seen in bronchoalveolar lavages and in biopsy specimens, suggesting that these cells did not increase at the sites of inflammation. These findings suggest that increased levels of gamma delta T cells in the peripheral blood occur in active, long-term sarcoidosis, but that they are not directly related to granuloma formation.