BACKGROUND Combination chemotherapy, including hybrid regimens, is the standard treatment for patients with advanced Hodgkin disease (HD). Although a prolonged complete response (CR) is achieved in up to 70–80% of patients, long term complications, such as secondary leukemia, are of concern. Cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (C‐MOPP/ABV) is a hybrid chemotherapy in which cyclophosphamide is substituted for mechlorethamine, an agent that has been implicated as the cause of secondary malignancies. METHODS Seventy‐three patients (37 males and 36 females; median age, 35 years) diagnosed with Stage III or IV HD or Stage II with bulky disease, B‐symptoms, elevated erythrocyte sedimentation rate, or hilar adenopathy were treated with 8 courses of C‐MOPP/ABV at a single institution during a 6‐year period. Radiotherapy (RT) was administered when bulky disease or residual masses were present. Endpoints of the study were response to therapy, failure free survival (FFS), overall survival (OS), and toxicity. RESULTS Sixty‐five patients (90%) received the 8 planned courses, with 49 of them (70%) receiving the full prescribed doses. After chemotherapy, 57 patients (78%) reached CR. Seven additional patients who achieved partial response (PR) reached CR after complementary radiotherapy, with an overall CR rate of 88%. The median follow‐up was 31 months. Twelve patients relapsed; the 4‐year FFS was 66% (95% CI, 54–78%). Two patients died during treatment because of sepsis and four due to disease progression. The 4‐year OS was 92% (95% CI, 86–98%). Age > 60 years and bone marrow involvement were related to severe infectious complications. No late toxicity was reported. CONCLUSIONS C‐MOPP/ABV induces CR with acceptable toxicity in a high proportion of advanced HD patients. Cancer 2000;88:2142–8. © 2000 American Cancer Society. Hybrid chemotherapy consisting of cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (C‐MOPP/ABV) as first‐line treatment for patients with advanced Hodgkin disease induces a high complete response rate with acceptable toxicity, especially in young patients.