The margin of safety of a drug is defined as the ratio between toxicity in animals and safety in humans. For intravascular contrast media, the margin of safety is traditionally the ratio between LD50 and diagnostic dose, both doses being based on bodyweight. The shift to surface area dramatically reduces this margin to unacceptable values. Toxicokinetics, which relates systemic exposure associated with early toxic signs in animals to plasma level in man, seems the most accurate and predictive criterion.