Previous studies have shown that interferon-α (IFN-α) and chemotherapy is an effective treatment for patients with newly diagnosed follicular lymphoma. Therefore, we performed a phase II trial to determine the safety and effectiveness of IFN-α and standard doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy (IABVD) in these patients. Patients with newly diagnosed advanced stage classic Hodgkin lymphoma (HL) were enrolled between July 1997 and March 2000 on IABVD as initial therapy. This consisted of six cycles of ABVD with concurrent IFN-α followed by radiation therapy if indicated. IFN-α 6 million IU/m(2) was administered subcutaneously daily for 3 days and on day 4 patients received IFN-α with ABVD. Courses were repeated every 2 weeks for a maximum of 12 courses. IFN-α dose reduction was allowed for cytopenia. Outcome and baseline characteristics were reported. Thirty patients (median age, 30 years [range, 18-62 years]) were evaluable. Patients had Ann Arbor stage II (7%), III (30%) or IV (63%) disease, and 47% were at intermediate or high risk, as defined by the International Prognostic Score (≤ 2 vs. > 2). The 3-year event-free survival rate was 71% (95% confidence interval [CI], 56-90%), and the 3-year overall survival rate was 96% (95% CI, 89-100%). Treatment was well tolerated, with only three patients requiring IFN-α dose reduction or discontinuation because of cytopenia. IABVD is an effective regimen against advanced HL and is well tolerated. However, because of the emergence of effective new biologic agents, further development of this regimen is not warranted.