Introduction: Direct current (DC) ablation offers the potential for precise targeting of tumors and stimulation of the immune system, but has not achieved widespread use. This study was conducted to evaluate the impact on tumor size and subject survival of combining a main ablation treatment with a low-current pretreatment, to assess potential immune system activation, and to assess stimulation-related parameters. Methods and Results: Twenty-six female Fischer 344 rats were injected with methylcholanthrene-induced fibrosarcoma cells to create primary tumors and again in the contralateral flank when primary tumors reached 700 mm3 (contralateral tumors were proxies for metastases). There were four treatment groups: two control animals received no treatment; six control plus placebo animals had electrodes implanted but received no stimulation; eight received high-current stimulation (80 coulombs (C) of charge at 20 milliamperes (mA), over 66 minutes); and eight received high-current treatment one day after a low-current pretreatment (10 C, 10 mA, 16.6 min). Electrodes were inserted through the tumor base in a single plane, 4.0 mm apart, alternating anode and cathode. Treatments commenced once primary tumors reached 700 mm3. All control animals were sacrificed 55 days after primary tumor cell injection due to excessive tumor growth. Tumors disappeared from all 16 treated rats within eight days; retreatment was required in two animals. Pretreatment had no effect on tumor disappearance or survival. Conclusion: Direct current ablation provides highly effective tumor destruction in a rat model. Slower growth of contralateral tumors suggests a remote effect that may involve the immune system.