Up to the beginning of the 1980s the surveys on adverse reactions to uro-angiographic, iodinated contrast media administered intravenously failed to recognize any significant correlation between the incidence of such reactions and the type and/or dose of administered compound. Consequently the role of pharmaco-toxicological characteristics of the different iodinated molecules was considered negligible in comparison with the individual risk factors causing for the systemic adverse reactions. More recent surveys have shown that the risk of severe adverse reactions is about six times lower with non-ionic than with ionic compounds. These clinical results confirm the findings of animal studies that showed a two- to three-fold greater safety margin for non-ionic compounds than ionic compounds. In view of these data, the predictive value of pre-clinical safety assessment of iodinated contrast agents is re-examined. The interspecies scaling approach is considered useful owing to the well-known and very simple pharmacokinetic behaviour of these compounds both in humans and in animals.