Spontaneously occurring agglutinins in animal sera are shown to fall into several categories, namely, 1. cold-reactive agglutinins; these often are nonspecific and act as autoagglutinins, 2. agglutinins reactive at room as well as refrigerator temperatures; these, like cold agglutinins, are usually IgM immunoglobulins which may be species-specific in their activity, or type-specific, notably, like anti-A and anti-B and 3. agglutinins reactive at body temperature, usually IgG immunoglobulins, and most often due to maternofetal incompatibility and transplacental immunization of the mother by fetal red cells. The naturally occurring cold autoantibodies are physiologic in nature and appear to be the raw materials for antibody production. This is postulated to be adaptive in nature by enzyme action, through in part genetically determined, as evidenced by the so-called constant polypeptide sections of the immunoglobulin molecules.