SummaryThe effects of the proteolytic enzyme bromelain (Br) on the antigenicity and immunogenicity of sheep and mouse red blood cells (RBC) have been investigated. The results presented support the previous claim that there are antigens present on Br RBC that are not present in an exposed form on untreated RBC and that Br RBC have lost some of the antigens present on the surface of normal RBC. The susceptibility of Br RBC to osmotic lysis was very similar to that of normal RBC. Implying that the modified RBC were not more fragile than normal RBC. Injection of mice with Br mouse‐RBC did not increase the unusually high “background” number of cells producing IgM antibodies against Br mouse‐RBC and mice did not mount delayed‐type hypersensitivity reactions against Br mouse‐RBC, either before or after sensitizing injections of Br mouse‐RBC. However, mouse‐RBC and Br mouse‐RBC elicited similar antibody responses in rabbits and guinea pigs. Although mice appeared unresponsive to Br mouse‐RBC injections, delayed‐type hypersensitivity responses and antibody production in primary and secondary responses were of similar levels irrespective of whether sheep‐BBC or Br sheep‐RBC were used as immunogens.From these studies it appears that mice have B‐cells producing antibodies against the “new” antigens on Br mouse‐RBC. But there are no T‐cells that respond to these antigens by way of “helper” activity in antibody production or by way of cell‐mediated immune reactions.