PURPOSE: We developed and evaluated a GM-CSF whole-cell tumor vaccine for esophageal cancer. EXPERIMENTAL DESIGN: Cell lines derived from surgically induced rat reflux esophageal tumors were passaged in vitro and transfected with GM-CSF. First, the GM-CSF whole cell vaccine was evaluated against subcutaneously transplanted esophageal tumor cells. In a subsequent study, the vaccine was tested to see if it could reduce the incidence of cancer in the surgical reflux model. RESULTS: While subcutaneously transplanted tumor cells produced lasting tumors in PBS non-vaccinated placebo rats, transplanted tumors regressed and were immunologically rejected in animals vaccinated prior to implantation. In the surgical reflux model, the vaccine reduced the incidence of cancer from 17/23 (74%) in the controls to 6/16 (38%) in the vaccinated animals (P = 0.046). CONCLUSIONS: The GM-CSF whole cell tumor vaccine effectively promoted a strong immune response against subcutaneously transplanted tumors and protected animals from developing esophageal cancer in the reflux model.