The causes for adverse reactions to radiographic contrast media (RCM) are unknown. Many theories have been proposed to explain the reactions but none are wholly satisfactory. The aim of this thesis has been to examine certain aspects of adverse contrast reactions in patients and laboratory animals in an attempt to cast light on the underlying mechanisms of the reactions, A potential predictive assay has been tested to assess its usefulness in identifying those patients at increased risk of an adverse reaction. (1) A clinical study has been undertaken involving the blood- sampling of reactors to radiographic contrast medium as well as control patients, in the Glasgow area over a period of three years. Each patient was questioned and a pro-forma filled out for the purposes of attempting to identify potential risk factors. The blood samples obtained formed the basis for most of the subsequent laboratory studies. The main conclusions from the data obtained via the questionnaire was that patients with a previous history of adverse contrast reaction or with an allergy history are at increased risk of a reaction. No other predictive pointers were found that would lead to identification of those at increased risk of a reaction. (2) One theory that has been proposed to explain contrast reactions is that contrast media may act as happens and that the adverse reactions are due to an antigen/antibody reaction. Brasch and colleagties from San Francisco have been the main proponents of this theory and have published data suggesting reactors to contrast media have specific anti-contrast antibodies in their sera and the same group have also induced antibodies to contrast media analogues in animals (Brasch and Caldwell, 1976; Brasch, Caldwell and Pudenberg, 1976). Other groups have failed to induce antibodies in experimental animals and have also failed to detect them in reactor patients (Lasser, 1968; Lasser, 1971; Bunn et al, 1975) view of the conflicting evidence, I felt it would be worthwhile to attempt to induce antibodies in rats using immunisation techniques developed in Glasgow which have been successful in the induction of IgE and also IgG antibodies (Jarrett and Stewart, 1974). I have also attempted to detect specific anti-contrast antibodies of the IgE and IgG classes in the sera of reactor and control patients using radioimmunoassays. The results of attempted induction of antibodies in rats were completely negative, suggesting that sodium/meglumine diatrizoate and meglumine ioglycamate do not act as haptens in this animal model. The results from the radioimmunoassays were negative also - IgG antibodies were detected but these were not specific for the contrast medium. (3) Changes in protein configuration induced by contrast media were sought using a fluorescence technique utilising 1-anilino- naphthalene-8-sulphonic acid (ANS) (Thompson and Yielding, 1968). The results were negative for all contrast media tested with human gammaglobulin and negative with all contrast media tested with human serum albumin apart from meglumine ioglycamate which altered the fluorescence, raising the possibility of alteration in configuration of the albumin. An alternative possibility is that the meglumine ioglycamate may have been competing with the ANS for binding sites on the protein. If meglumine ioglycamate did, in fact, alter the configuration of the albumin, it is conceivable that the modified albumin may have, in fact, become antigenic. (4) Studies into the effect of contrast media on neutrophil enzyme release and neutrophil locomotion have been carried out and have demonstrated that contrast media have significant effects on both neutrophil enzjnnae release and neutrophil locomotion suggesting that contrast media can alter the permeability and/or composition of neutrophil cell membranes. This may be relevant, in that if contrast media can alter cell membrane permeability, then the cells may release toxic mediators and activators, e.g. kinins and proteases.