Sarcoidosis is a systemic disorder characterized by the accumulation of a large number of T-lymphocytes in pulmonary sites. Considerable evidence has been presented that alveolar lymphocytes are activated by some agent in pulmonary sarcoidosis, although the pathogenesis of this disease remains unknown.The proliferation of lymphocytes, obtained by bronchoalveolar lavage, was determined by in vitro incorporation of 3H-thymidine induced by Propionibacterium acnes (P.acnes).The mean response rate of alveolar lymphocytes was 1.91±0.80 in 22 untreated sarcoidosis patients, 1.22±0.46 in nine sarcoidosis patients given prednisolone, and 0.90±0.39 in 15 controls. The response rate was significantly enhanced in untreated patients compared to both treated patients (P<0.01) and controls (P<0.001), and a significant difference was noted in the response rates between treated patients and controls. The response rate of alveolar lymphocytes in seven patients with active sarcoidosis (2.76±0.63) was significantly higher than that in 15 patients with inactive sarcoidosis (1.15±0.50)(P<0.05) and in the controls (P<0.01). In sarcoidosis patients, the response rates showed a good correlation with the activities of serum lysozyme (r=0.523, P<0.01), with percentages of lymphocytes present in bronchoalveolar fluid (r=0.537, P<0.01), as well as angiotensin-converting enzyme activities (r=0.436, P<0.05). The alveolar lymphocyte response rates induced by P. acnes reflect the disease activity of sarcoidosis. Neither peripheral lymphocytes in the sarcoidosis patients nor those in the controls showed a response to P. acnes. Those results suggest that alveolar lymphocytes in untreated patients with active sarcoidosis are sensitized by P. acnes, and that activated lymphocytes play a central role in the induction of alveolitis in sarcoidosis patients through P. acnes.