Fifteen patients with lymphomatoid granulomatosis were studied prospectively over a 10-year period. Thirteen of the patients received the therapeutic protocol of cyclophosphamide (2 mg per kilogram of body weight per day) and prednisone (1 mg per kilogram on alternate days). Previous reports had indicated that mortality from lymphomatoid granulomatosis was as high as 90 per cent. Of the 13 patients who received the cyclophosphamide and prednisone protocol, seven had complete remissions lasting for 5.2 +/- 0.6 years (mean +/- S.E.M.) Six of the seven with disease in remission have received no therapy for 28.3 +/- 5.7 months. Malignant lymphomas developed in seven of the eight who died, and only two of the eight had therapy for an adequate period. Since virtually all patients who did not have complete remission went on to have malignant lymphoma, early recognition and prompt treatment during the lymphomatoid-granulomatosis phase of disease may not only lead to complete remissions but also percent the development of a lymphoid neoplasm.