Until the mid 1960s the advanced stage, high grade non-Hodgkin's lymphomas were rapidly progressive, fatal diseases with few patients remaining alive at 5 years. Studies conducted at the NCI demonstrated that 47% of all patients with advanced stages of diffuse mixed, large cell, and undifferentiated non-Burkitt's lymphoma could achieve a complete remission documented by reevaluation of all initially involved sites following treatment with either the C-MOPP or BACOP combination chemotherapy regimens. Furthermore, 70% to 80% of these complete responders had long-term disease-free survival tan-tamount to cure. The third generation of NCI studies, termed the ProMACE-MOPP flexible induction program, significantly improved these results. Complete remissions were achieved in 74% of all patients and 73% of these remain disease free in excess of 3 years. Myelosuppression was dose limiting with a 10% septic death rate. Studies are currently underway in an attempt to minimize the toxicity of the new regimen, while preserving the increased complete response rates and long-term survival.