In this article I shall be concerned almost exclusively with theoretical as-pects ofimmunity. Medawar has spo-ken of the experimental aspects of ac-quired immunological tolerance and other types of immunological nonreac-tivity, and he has touched on the impossibility, in natural chimeras, of demonstrating that the genetically alien cells are treated in any way differently from cells that are genetically proper to the body. For me, acquired immunological tolerance means simply that the con-tent of self-components in the body has been enlarged by an experimental ma-nipulation. Basically, I shall deal in this article with a single problem: How does the vertebrate organism recognize self from not-self (in the immunological sense), and how did this capacity evolve?