Natural‘antibodies’are substances found in the blood of animals that have not been immunised against infective agents. However, exposure to these agents or to cross‐reacting antigens may well have taken place. Fish contain naturally‐occurring, relatively nonspecific, lectin‐like proteins or glycoproteins, which are distinct from immunoglobulins, and which react with a wide variety of antigens and may confer some degree of immunity against natural infection. In most cases the cause of the antigenic stimulus is not obvious although the formation of these‘antibodies’may have been brought about by exposure to various micro‐organisms. Many of these antibody‐like molecules behave in a similar manner to immune antibodies or immunoglobulins and cross‐react with specific carbohydrate moieties on the cell walls of bacteria, erythrocytes and certain other cellular antigens, due to the presence of similar antigenic determinants.It is difficult to ascribe an appropriate definition to the term‘natural antibody’. In fish, these‘antibodies’have been so designated on the basis of functional rather than structural criteria. Such naturally‐occurring, low grade, antibody‐like‘immune’substances include‘acute phase’proteins, lysozyme and chitinase, interferon, agglutinins, lysins, complement and properdin, precipitins, and non‐immunoglobulin, lectin‐like molecules. In addition to the above non‐immunoglobulin materials, natural immunoglobulins identifiable as IgM have also been reported in fish. Furthermore, mucus contains many biochemical agents capable of reaction against infective organisms and thus providing the host with an immediate or a first line of defence mechanism.This review compiles some of the relevant information in the literature concerned with natural‘immune’substances, present in the serum and mucus of fish, involved in protection against pathogens. Wherever possible the basic physicochemical properties of these substances are indicated and the