The paradoxical features of transplantation specificity—its strict genetic control in transfers of tissue from strain to strain as compared with its malleability on tissue passage in foreign immunological environments where the host does not reject the implant (F₁ hybrid passage, tolerance actively acquired by immature hosts, and so on)—present a challenge to genetic interpretation. The attempt is made in this article to show parallels between this behavior and such changes as the transformation of serotypes in Paramecium, in which the activity of genetic units becomes fixed as a cytoplasmic state—a cellular heredity persistent under specified environmental conditions but capable of change to an alternative state—while the genetic structure of the cell remains constant. The reactions appear to differ from those in the Paramecium case in that the diverse loci control a mosaic of different specificities, which change relatively independently of each other, in contrast to mutual exclusion of cytoplasmic states influenced by the different loci in Paramecium.

The process of antibody formation is considered as a change in cellular phenotype from the same point of view. The primary response in the stem cells of the lymphoid tissues is interpretable as the establishment of a new cytoplasmic state in response to a nuclear stimulus by the foreign antigen. For the secondary response, the suggestion is made that a reaction of antigen with cellular antibody at the surface of stem cells exhibiting the primary response serves as the stimulus for specific proliferation of antibody-forming clones of cells. A parallel is drawn with the fertilization reaction, specifically with regard to the initiation of cleavage in eggs by antisera to them.

Finally, a general chromosomal mechanism is sought for these phenomena, on the basis of activities of specific chromosome regions in response to special developmental stimuli, such as the disproportionate local synthesis of deoxyribonucleic acid demonstrated in the giant chromosomes of the Diptera. By a correlation of such activities with the nucleocytoplasmic system of ribonucleic acid granules on membranes, a possible mechanism appears for the formation, in response to environmental stimuli, of cytoplasmic states which might supply the persistent pattern required for this type of cell heredity. The analogies made, it is believed, provide a framework for the design of test experiments.