Mutations in the p53 tumor suppressor gene giving rise to mutant p53 proteins are among the most common genetic alterations associated with tumor cells. Mutant p53 gene products lose the wild type ability to suppress transformation in vitro or regulate cellular gene transcription. Mutant and wild type p53 protein conformations differ and mutant p53 is often present at high levels in the tumor cell relative to the low levels found in normal cells. Despite the major advances made to characterize the structure and biology of mutant and wild type p53, the humoral immune response against mutant p53s remains to be clearly defined. In the present study we have examined the anti-p53 response from cancer patients against the native and denatured state of mutant and wild type p53. Western blot analysis, immunoprecipitation analysis, and dilution analysis demonstrate that the anti-p53 sera recognize both wild type and mutant p53 conformational and denaturation resistant epitopes. There was no evidence that the mutant p53 molecules contain dominant antigenic epitopes which are not present on the wild type p53 protein. We also demonstrate that patients with ovarian cancer are also among those which can produce anti-p53 antibodies.