Background: The local cellular immunity is responsible for the pathogenesis and development of disease in the affected organ. In tuberculous pleurisy lymphocytes are principally involved in cellular immunity. This immune response is specially mediated by Th1 and its related cytokines. In laboratory investigations all of the interleukins associated with Th1 axis, such as interferon gamma, are 20-60 times higher in pleural fluid as compared to blood. This significant increase in lymphocytes of the pleural fluid as compared to blood is a strong evidence for the compartmentalization of cytokines of Th1 axis in pleura, resulting in an appropriate and satisfactory immune response to mycobacterial infections. PPD reaction test (Mantoux test) is a delayed hypersensitivity reaction in skin in which cellular immunity and Th1 axis are responsible. It seems that compartmentalization of CD4+ T cells is effective in response to Mantoux test in patients suffering from tuberculous pleurisy.This study was conducted either to prove or refuse this hypothesis. Materials and Methods: This was a 2-year cross-sectional study in which we studied the status of lymphocyte subgroups by flowcytometry in peripheral blood and pleural fluid of patients with pleurisy in which lymphocytes are principally involved. We also evaluated and compared its relation with Mantoux reaction test. Results: Overall, 36 patients with pleurisy in which lymphocytes were principally involved in their pleural fluid entered the study. Out of them, 25 suffered from tuberculous pleurisy. In the tuberculous pleurisy group (25), 17 (68%) had positive Mantoux test while in 8 cases (32%), this test was negative. There were 31 males (86%) and 5 females (14%) with the age range of 17 to 60 yrs and the mean age of 35 years. In the PPD negative group the CD4+ count was significantly high in the pleural fluid. However, in PPD positive cases the CD4+ count was less significant but was still significantly higher in pleural fluid as compared to peripheral blood (p < 0.05). In PPD negative group CD8+ lymphocytes were significantly in a higher level than in blood. This was not seen in PPD positive group. Conclusion: Cellular immunity is the main local response in these patients. As it is seen majority of cells present in the pleural fluid are CD4 and CD8 lymphocytes. CD19+ lymphocytes are in minority. The dominance of CD4+ lymphocytes in pleural fluid of PPD negative and PPD positive groups is a sign of Th1 compartmentalization in this disease. But, the important difference between these two groups is the dominance of CD8+ lymphocytes in peripheral blood of PPD negative cases and the CD4+/CD8+ ratio in pleura and blood of PPD positive cases are close to each other. It means that the difference between the CD4+ and CD8+ counts in the pleural fluid and blood is significantly higher in PPD negative group compared to the PPD positive one. This difference indicates the effective role of compartmentalization of active CD4+ lymphocytes of pleura in response to Mantoux test, as some studies suggest that cutaneous anergy is due to aggregation of active lymphocytes in pleural fluid. Secondly, according to the accumulation of lymphocytes in pleura and considerable difference in the type of lymphocytes in peripheral blood and pleura, obtaining Paraclinical data related to disease (specially ADA) only by evaluating the blood is not appropriate. This fact is confirmed in other studies as well. (Tanaffos 2005; 4(13): 57-62)