We conducted a multi-center phase II trial of gemcitabine (G), carboplatin (C), dexamethasone (D), and rituximab (R) in order to examine its safety and efficacy as an outpatient salvage regimen for lymphoma. Fifty-one patients received 2-4 21-day cycles of G (1000 mg/m(2), days 1 and 8), C (AUC = 5, day 1), D (40 mg, daily days 1-4), and R (375 mg/m(2), day 8 for CD20-positive disease) and were evaluable for response. Characteristics included: median age 58 years (19-79 years), stage III/IV 88%, elevated LDH 33%, median prior therapies 2, prior stem cell transplant 12%, chemoresistant 62%, median prior remission duration 2.5 months. The overall and complete response rates were 67% (95% confidence interval [CI] 54-80%) and 31% (95% CI 19-44%), respectively, with activity seen in a broad variety of histologies. Responses occurred in 16 of 17 (94%, 95% CI 83-100%) transplant-eligible patients and 15 of 28 (54%, 95% CI 34-71%) with chemoresistant disease. The median CD34 yield in patients attempting peripheral blood stem cell (PBSC) collection following this regimen was 10.9 x 10(6) CD34+ cells/kg (range 5.0-24.1 x 10(6)). Hematologic toxicity was common, but febrile neutropenia (2.5%) and grade 4 non-hematologic adverse events (n = 2) were rare, with no treatment-related deaths. GCD(R) is a safe and effective outpatient regimen for relapsed lymphoma, and successfully mobilizes PBSCs.