The discovery of dendritic cells (DC) as professional antigen presenting cells has opened up new possibilities for their use in the development of cancer vaccines. Here we show that unpulsed BM-derived CD11c+CD8alpha-DC administered s.c. to mice enhanced their resistance to subsequent lethal tumor challenges. The tumor resistance-inducing activity of unpulsed DC was dependent on their maturation status, involved CD4+ and CD8+ T cell activities, and was abrogated by pulsing with an irrelevant class I MHC-restricted peptide. Although the BALB/c Meth A tumor system was employed extensively to demonstrate the tumor resistance inducing activity of unpulsed DC, the immunogenicity of this vaccine was evident in other inbred strains of mice against a variety of syngeneic tumors. The broad anti-tumor responses induced by unpulsed DC appears to be due to their capacity to present "self" tumor-associated antigens, such as the H2-Kd-restricted, wild type sequence p53(232-240) peptide. These findings highlight the potential broad applicability of unpulsed DC as a tumor vaccine.