Vaccination with tumor extracts circumvents the need to identify specific tumor rejection antigens and extends the use of active immunotherapy to the vast majority of cancers, in which specific tumor antigens have not yet been identified. In this study we examined the efficacy of tumor vaccines comprised of unfractionated tumor material presented by professional antigen‐presenting cells (APC): dendritic cells (DC) or macrophages (Mø). To enhance the relevance of these studies for human patients we used 2 poorly immunogenic murine tumor models and evaluated and effectiveness of the vaccination protocols in tumor‐bearing animals. APC (in particular DC) pulsed with unfractionated extracts from these “poorly immunogenic” tumors were highly effective in eliciting tumor‐specific cytotoxic T lymphocytes. A measurable CTL response could be detected after even a single immunization with tumor extract‐pulsed DC. DC or Mø pulsed with tumor extract were also effective vaccines in tumor‐bearing animals. In the murine bladder tumor (MBT‐2) model a modest extension of survival and 45% cure rate was seen in the animal groups immunized with DC or Mø pulsed with MBT‐2 tumor extract. DC or Mø pulsed with B16/F10.9 tumor extract were also remarkably effective in the B16 melanoma lung metastasis model, as shown by the observation that treatment with APC caused a significant reduction in lung metastases. Cumulatively, the CTL and immunotherapy data from the two murine tumor systems suggest that APC (in particular DC) pulsed with unfractionated cell extracts as a source of tumor antigen may be equally or more effective than genetically modified tumor vaccines. Int. J. Cancer 70:706–715, 1997. © 1997 Wiley‐Liss, Inc.