In 1987, we reported three patients with pleural lymphoma developed after a 22-30 year history of pyothorax resulting from artificial pneumothorax for the treatment of pulmonary tuberculosis or tuberculous pleuritis. Based on the pathologic and epidemiologic studies, we regarded the chronic pyothorax (CP) to be etiologically important in the development of pleural lymphoma. Through a nation-wide study in Japan, 37 cases of pleural lymphoma were collected. Pleural lymphoma had developed during the 20 year history of CP in all patients. Histologically all were non-Hodgkin's lymphoma with the diffuse large cell type being the most common. Immunologic and immunohistochemical studies revealed that 32 out of 33 cases were of B-cell lymphoma. From these findings, we proposed the term pyothorax-associated lymphoma (PAL). We examined the presence of Epstein-Barr virus (EBV) genome on the paraffin-embedded specimens in 34 PAL cases and 16 cases of CP alone. Combined polymerase chain reaction (PCR), in situ hybridization, and immunohistochemistry revealed that the EBV genome was detected in lymphoma cells in all PAL, but only one of the cases with CP alone. These findings suggested the etiological role of EBV for the development of PAL. We also described here the character of cell lines established from PAL, association of PAL with Kaposi's sarcoma-associated herpes virus, results of a case-control study on risk factors for development of PAL, and p53 mutations.