The purpose of this study was to evaluate the efficacy and toxicity of an intensified dose protocol with no maintenance phase for the treatment of canine lymphoma. Forty-nine dogs all weighing more than 15 kg were entered. Dogs were staged and treated with a modified version of the University of Wisconsin (UW)-Madison protocol for lymphoma. Modifications included increased dosages of cyclophosphamide (250 mg/m2 compared to 200 mg/m2) and doxorubicin (37.5 mg/m2 compared to 30 mg/m2), with no crossover to chlorambucil or methotrexate. After 25 weeks on protocol (17 treatments), therapy was discontinued and dogs were monitored for relapse on a monthly basis. Disease-free interval (DFI) and overall survival were compared to 55 historical controls treated with the UW-Madison protocol. The 2 groups were comparable with respect to age, sex, breed, stage, presence of hypercalcemia, and CD3 status; a trend toward more substage b dogs was present in the high-dose group (P = .076). When comparing response rate, DFI, death due to disease, and death due to treatment-related toxicity, more dogs were dead due to toxicity (P < .001; odds ratio = 8.8) in the high-dose group. Overall survival between the high-dose and control groups did not differ significantly (P = .55) at 270 and 318 days, respectively. The intensified dose protocol is an option for owners who are willing to risk higher toxicity for a shorter protocol with no statistical difference in survival from the UW-Madison protocol.