Pleural tissues from a group of 36 consecutive patients comprised of 15 malignancies, 3 tuberculous, 2 rheumatoid arthritis, 3 procainamide-induced systemic lupus erythematosus (SLE) syndromes, 1 infectious mononucleosis, and 12 nonspecific pleural effusions undergoing needle biopsy were studied by immunofluorescent techniques for antibody deposition. Specific nuclear fluorescence was detected only in procainamide-induced SLE and was characterized by in vivo staining with either IgG, IgM, and in one case, also C3. C1q could not be detected. Two other patients who had antinuclear antibodies (ANA) in their peripheral blood did not have detectable in vivo antinuclear staining in their pleural tissue. The presence of in vivo fixation of ANA in the pleura may be of etiologic and diagnostic significance in procainamide-induced SLE syndrome.