In preclinical models, tumor cells genetically modified to express cytokines or other costimulatory molecules can generate systemic antitumor immunity. In some cases, these tumor vaccines have been shown to eradicate micrometastases. These results have led to the initiation of numerous phase I clinical trials employing either autologous or allogeneic tumor vaccines genetically modified to express cytokines and other genes. In this report, we use our murine model to identify a number of parameters that may be critical for enhancing vaccine efficacy. In addition to antigen dose and cytokine level, the distribution of vaccine inoculation was found to have a significant impact on vaccine potency. These results require consideration in early clinical trials designed to evaluate cellular vaccine therapy.