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The peripheral blood lymphocytes from 43 patients with sarcoidosis were cultured in the presence of various stimuli. Uptake of thymidine-3H was employed as a measure of in vitro DNA synthesis. The spontaneous DNA synthesis of lymphocytes from cases of sarcoidosis was slightly increased when compared with that of control cells. On the other hand, the response to phytohemagglutinin from control cells and that from cells of patients with sarcoidosis were not significantly different. Lymphocytes from patients with sarcoidosis exhibiting negative skin tests to tuberculin (PPD) failed to respond to that antigen in vitro whereas those from patients with a positive skin test showed an uptake of thymidine-3H which was similar to that of PPD positive controls. Lymphocytes from patients with sarcoidosis previously vaccinated with polio antigen, were shown to be stimulated in vitro by this specific antigen. A mitogenic factor (MF), prepared by incubating lymphocytes from patients highly sensitive to PPD antigen, was shown to induce DNA synthesis in vitro in lymphocytes from healthy donors, whether or not they were tuberculin sensitive, as well as in lymphocytes from patients with sarcoidosis. On these 3 populations of cells, a non-specific stimulatory effect was also demonstrated in vitro, with the use of pooled sera from patients with active pulmonary tuberculosis. Finally, testing the role of macrophages, it was shown that incubation of control sensitized macrophages with lymphocytes from patients with sarcoidosis, failed to reverse the unresponsiveness of these lymphocytes in the presence of tuberculin.