- Pleural involvement is the most frequent manifestation of rheumatoid arthritis (RA) in the chest. We report here two patients who presented with large exudative pleural effusions and subsequently developed sero-positive RA. In both cases, the differential cell count of the pleural effusion suggested empyema. A literature review identified that RA-associated pleural effusion afflicts more men than women and 95% of the patients have high titers of rheumatoid factor (RF). In 46% of cases, RA-associated pleural effusion is diagnosed in close temporal relationship with the diagnosis of RA. The effusion is an exudate and is characterized by low pH and glucose level, and high lactic dehydrogenase (LDH) and cell count. At diagnosis there is a tendency for predominant neutrophils to occur consistent with an empyema and 7-11 days later, the cells in the pleural effusion are replaced by lymphocytes. Pleural effusion with predominant eosinophilia is rare. RA patients with acidic effusion and low glucose content with neutrophils predominance should be treated with thoracic drainage and antibiotics until an infection is ruled out. The histo-pathologic findings in pleural fluid of tadpole cells and multinucleated giant cells and the replacement of the mesothelial cells on the parietal pleural surface with a palisade of macrophage derived cells are described as pathogonomic for RA. Treatment with systemic steroids and intra-pleural steroids are effective in most cases.