AbstractEleven patients with Hodgkin's disease refractory to chemotherapy were treated with six cycles of intermediate‐dose methotrexate with calcium leucovorin rescue, followed by cyclophosphamide, doxorubicin, vincristine, and prednisone (MTX‐CHOP). Three other patients were treated with a similar program of treatment minus doxorubicin (MTX‐COP). The overall response rate was 57%, with four (29%) patients achieving a complete response and four patients achieving a partial response. None of the three patients treated with MTX‐COP had a complete remission (CR); thus the complete remission rate with MTX‐CHOP was somewhat higher (36%). Only one of the CR's is in continuous complete remission and free of disease at 99+ months. One patient died of overwhelming sepsis and pancytopenia during treatment. Hematologic toxicity in the other patients was acceptable. The overall median survival was 18 months. The search for an effective treatment program for this group of patients remains a major