Only very few immunological publications are based on investigations using non-mammalian vertebrates as experimental animals. Nevertheless, some important immunological problems, such as dichotomy of T and B lymphocytes or immune tolerance, were first discovered or even solved using such species. The usefulness of comparative investigations with species of different vertebrate classes is shown, referring to our own investigations of organ transplantations in the 1950s and of the regulation of the IgM antibody response in the last years.