Combination chemotherapy with four drugs—nitrogen mustard, vincristine, procarbazine and prednisone—was used in 27 previously treated patients with advanced progressive Hodgkin’s disease. Six 2-week cycles of chemotherapy were administered in the following schedule: nitrogen mustard, 6 mg./sq.M. I.V., and vincristine, 1.4 mg./sq.M. I.V., on days 1 and 8 of each cycle; procarbazine, 100 mg./sq.M. by mouth daily throughout each cycle, and prednisone, 40 mg./sq.M. orally each day of cycles 1 and 4. Each cycle was followed by a 2-week period during which no drug was given. Twenty-two patients had Stage IV disease and 17 had systemic symptoms at the time of drug administration. All patients had histories of previous therapy. Two received chemotherapy alone, 15 had radiotherapy alone and 10 had both chemotherapy and radiotherapy. Nineteen out of the 27 patients (70%) had complete responses (total regression of all lesions) to the four drug combination and five patients (19%) had partial responses (50% regression of all lesions). Fourteen out of the 19 who responded completely are still in unmaintained remission 1-24 months from therapy completion. Eighteen out of the 19 who responded completely are still surviving from 6 to 30 months after the start of combination chemotherapy. Those patients treated previously with both radiotherapy and chemotherapy did not respond as well as patients treated with prior radiotherapy alone. In general, therapy was well tolerated, with leukopenia being the major dosage-limiting toxicity. There was a progressively poorer tolerance to the drugs with increasing extent of prior radiotherapy.