With the increasing use of beryllium (Be) and its alloys in various industries, beryllium lung disease will continue to present an important occupational health hazard. The disease occurs in acute and chronic form, and in both, lung injury dominates the clinical pathologic picture. While the direct toxic effect of Be is responsible for the acute form, there is still great controversy regarding the mechanism in the chronic form. Our studies during the past four years have provided direct evidence for participation of cellular immune mechanisms in the chronic form of the disease. Using currently accepted parameters for cellular immunity, such as lymphocyte blast transformation and release of migration inhibitory factor (MIF), we have shown that majority (75%) of patients with this disease have significant positive results and good correlation with clinical severity of the disease. In the proposed continuation of this project we wish to explore the possibility that these procedures can be used as screening tests for detecting beryllium industry workers who may be at high risk and for differential diagnostic studies of patients with other granulomatous diseases, particularly sarcoidosis. At the present time, a reliable test to differentiate between sarcoidosis and chronic berylliosis is not available. During the proposed three year period, we plan to study between 150 to 200 patients with sarcoidosis by the blast transformation test as described. On the experimental level, we have been able to produce the disease in a reproducible fashion in guinea pigs by intratracheal injections of beryllium oxide. We now propose the study of the effect of various immunosuppressive regimens, particularly of induction of tolerance to beryllium salts on the course of this disease. Our preliminary experiments have been very encouraging and we feel that continued experiments along this line will provide the most direct evidence for participation of immune mechanisms.