Since the time of Paul Ehrlich 100 years ago, we have known that the i
mmunological apparatus somehow inhibits most damaging autoimmune respo
nses while permitting a response to exogenous immunogens. With the dis
covery of tolerance, the concept of immunological surveillance, and es
pecially with the discovery of HLA restriction of T-cell recognition,
the term ''the immunological self'' and the phrase ''self-non-self dis
crimination'' have gained wide currency. Immunology has been called ''
The Science of Self'', and self-nonself discrimination has been assign
ed as the driving force for its complex evolution. The concept of self
has thus been given such mystical trappings since the time of Macfarl
ane Burnet that recent workers have felt free to pronounce it the cent
ral paradigm of modern immunology, and to claim to overthrow it! In th
is article, we challenge some of the more egregious claims about the i
mmunological self by recalling important historical findings, by revie
wing the mechanisms of Darwinian evolution, and by remembering that th
e general pathology of immunogenic inflammation shows that the immune
response cannot discriminate between the benign and the noxious.