Non-Hodgkin's lymphoma localized to the mediastinum and adjacent structures occurred in 12 of 215 (6+) non-Hodgkin's lymphoma patients seen at the Massachusetts General Hospital between 1975 and 1979. Lymphangiography, radionuclide scanning and whole body computerized tomography were used to exclude patients with extrathoracic disease at presentation. Eleven of the 12 patients presented with extensive contiguous extranodal disease (Stage IIE) with involvement of either the pericardium, sternum, chest wall, pulmonary parenchyma or, in four cases, with superior venacaval obstruction. Diffuse large cell lymphoma (eight cases) and diffuse poorly differentiated lymphocytic lymphoma (four cases) were the prevalent histologic subtypes; no instances of lymphoblastic lymphoma without extrathoracic spread were encountered. None of four lymphomas studied could be characterized as either B- or T-cell tumors utilizing conventional surface marker techniques. Ten of the 12 patients achieved complete remissions, either after treatment with combination chemotherapy alone (three patients) or after both chemotherapy and mediastinal irradiation (seven patients). Two of these ten have subsequently relapsed, but median survival has not been reached after a mean period of observation of 28 months. Primary nonlymphoblastic non-Hodgkin's lymphoma of the mediastinum is more common than previously realized, displays aggressive contiguous spread within the chest and responds well to combination chemotherapy with or without adjuvant mediastinal irradiation.