The substitution of chlorambucil for nitrogen mustard and vinblastine for vincristine has been suggested to be an equally effective and well-tolerated variation of the MOPP regimen (mechlorethamine, vincristine, procarbazine, and prednisone). We treated 76 patients with advanced (i.e., Stage III, IV, or II with bulky mediastinal mass) or recurrent Hodgkin's disease with chlorambucil 6 mg/m2, procarbazine 100 mg/m2, and prednisone 40 mg p.o. daily, all on days 1-14; plus vinblastine 6 mg/m2 i.v. on day 1 and 8 of each 28-day cycle (ChlVPP). There was no maximum dose of the myelosuppressive agents. Patients who had not previously been irradiated received from 2,300 to 4,100 cGY to sites of previously bulky diseases after completing 6 cycles of ChlVPP. ChlVPP was easy to administer (i.e., 87% of patients without previous chemotherapy received greater than or equal to 80% of the planned doses of myelosuppressive drugs) and was generally well tolerated, with only occasional vomiting from procarbazine and phlebitis from vinblastine. In patients without previous chemotherapy, 49 (76%) achieved a complete remission (CR) and 7 (11%) a stable partial remission (i.e., residual, stable radiographic abnormality). With a maximum follow-up of 4 years, only one CR has relapsed for an actuarial CR durability of 97%. ChlVPP with consolidative radiation therapy to sites of bulky disease is effective in advanced Hodgkin's disease and, compared with most other available regimens, is extremely well tolerated.