Total parenteral nutrition (TPN) has been suggested as a useful addition to chemotherapy of malignant disease in the hope of decreasing drug toxicity and increasing drug tolerance. In this study, 17 of 36 patients given chemotherapy for advanced diffuse lymphoma were randomly selected to receive TPN. The dose of the chemotherapeutic agents to be administered was decreased according to predetermined toxicity guidelines. A comparison of drug dosage in the group receiving TPN and the group receiving standard nutrition is a measure of drug tolerance in these patients. Drug dosage was evaluable in 15 TPN and 18 standard nutrition patients. No difference in tolerance of any specific drug or total drug dose occurred when all patients in both groups were compared. Similar comparisons in subgroups of malnourished patients and responding patients also revealed no difference. A cycle-by-cycle analysis demonstrated no difference in any phase of therapy. The wbc count, platelet count, and albumin level, on the first day of each cycle, the nadir during cycles and the day of nadir were compared in TPN and standard nutrition patients. No differences were found. This study does not suggest improved drug tolerance in lymphoma patients as a result of TPN support. Further controlled studies are needed to determine which groups of cancer patients might benefit from TPN and how these benefits occur.