Pleuropulmonary syndromes secondary to Waldenstrom's macroglobulinemia (WMG) are a distinct clinical entity which has received scant recognition. This review of 20 patients with WMG revealed five with pulmonary involvement. The radiographic abnormalities included one patient with a unilateral pleural effusion, and four patients with multiple asymmetrical nodular infiltrates in both lungs. Four patients had abnormal chest x-ray films at the time of diagnosis of WMG and these included two patients in whom the abnormal chest x-ray picture preceded the diagnosis of WMG by two and six years. Three patients had no respiratory symptoms, but cough and dyspnea were the chief complaints of the remaining two. The serum IGM level was elevated in all patients with a mean of 3.3 gm per deciliter. The classic features of WMG were frequently absent. Four patients presented with abnormal chest x-ray pictures in the absence of lymphadenopathy, hepatosplenomegaly, and ocular changes and included two patients who were not anemic. Pulmonary biopsy or necropsy specimens from four patients showed an infiltration of lung, pleura, or hilar lymph nodes by lymphocytes and plasmacytoid forms. The infiltrate tended to be patchy with sheets of lymphocytes replacing the lung parenchima. In some areas, the lymphocytic infiltrate was exclusively interstitial mimicing the histologic pattern of lymphocytic interstitial pneumonia. In the absence of therapy the pulmonary abnormalities were insidiously progressive over years. Three of the four patients treated with chlorambucil achieved significant radiographic clearing in one to three months. One patient died from diffuse pulmonary involvement in her eighth year of chlorambucil therapy.