Among 28 inpatients receiving antituberculous chemotherapies including isoniazid (INH) and rifampicin, we found 2 patients with newly developing pleural effusion in the hemithorax during the initial phase of successful chemotherapy. The analysis of the effusion fluids revealed an elevated level of antinuclear antibody and a decreased level of total component, which are findings compatible with lupus pleuritis. The peripheral lymphocyte stimulation test using INH was positive in 1 patient. To the best of our knowledge, there has been no published discussion of the relationship between a paradoxical response to antituberculous treatment and INH-induced lupus.