Management of patients with multiple-relapsed lymphoma meets with little success. The optimal use of available drugs in this situation is often unknown. Gemcitabine has documented efficacy in this setting. Pharmacodynamic data suggest that the optimal use may involve a fixed-rate infusion and coadministration with platinum compounds. In this study we explored the use of gemcitabine starting at a dose of 800 mg/m(2) administered at a fixed infusion rate of 10 mg/m(2) per minute with cisplatin 35 mg/m(2) intravenously, both given on day 1, and dexamethasone 20 mg daily for 4 days; the treatment was given every 2 weeks (days 1 and 15 of a 28-day cycle) for the treatment of relapsed Hodgkin's and non-Hodgkin's lymphoma. Dose escalation of gemcitabine was allowed according to phase I criteria. Twenty-two patients with a median of 4 prior treatments were enrolled (Hodgkin's lymphoma, n = 7; B-cell non-Hodgkin's lymphoma, n = 9; T-cell non-Hodgkin's lymphoma, n = 6). Ten patients had relapsed after prior autologous transplantation. Grade 4 thrombocytopenia and neutropenia were the dose-limiting toxicities and occurred in 9 patients (41%) and 4 patients (18%), respectively. Initial dose escalation of gemcitabine was not possible. Responses were observed in 45% of the patients: 2 of 5 with T-cell non-Hodgkin's lymphoma (1 patient withdrew after first treatment and was evaluable only for toxicity), 4 of 7 with Hodgkin's lymphoma, and 4 of 9 with B-cell non-Hodgkin's lymphoma. The coadministration of gemcitabine 800 mg over 80 minutes with low-dose cisplatin and dexamethasone is feasible and sufficiently active in a heavily pretreated patient population with lymphoma.