T-lymphocytes previously sensitized by an antigen undergo blastic transformation and produce IFN tau when stimulated by the same antigen. We studied the lymphoblastic response to PPD and IFN tau production in pleural fluid and peripheral blood of 41 patients (15 with tuberculous pleural effusion, 13 with nontuberculous pleurisy and positive tuberculin skin test, and 13 with tuberculin-negative nontuberculous pleurisy). In tuberculous pleuritis, pleural lymphocyte blastic response and IFN tau production were higher than those of peripheral lymphocytes, whereas in tuberculin-positive nontuberculous patients, peripheral lymphocyte response and IFN tau production were higher than those of pleural lymphocytes. Tuberculous pleural fluid lymphocytes underwent greater blastic transformation and produced more IFN tau than pleural lymphocytes of tuberculin-positive nontuberculous patients, whereas the opposite occurred in peripheral lymphocytes. In tuberculin-negative nontuberculous patients, there was no lymphoblastic response in either the pleural fluid or peripheral blood. These results concur with the concept of immunologic compartmentalization. In tuberculous pleuritis, there would be clonal expansion of PPD-responding T-lymphocytes in the pleural compartment. This expansion of PPD-specific lymphocytes would not occur in nontuberculous pleuritis, but lymphocytes sensitized to other antigens would accumulate in the pleural compartment.