(I.) Toxicity of ionic coronary arteriography contrast media has been shown to depend on their cationic and anionic composition and their osmolality. Using a right coronary injection technique in the dog, the authors have shown a relationship between toxicity as manifested by occurrence of ventricular fibrillation and the presence of calcium binders in the contrast media. Sodium citrate and EDTA have been identified as the specific agents in certain contrast media that significantly increase the incidence of fibrillation in laboratory experiments. (II.) A deleterious synergism between water-soluble angiographic and urographic media and digitalis compounds has now been demonstrated, based on mortality studies (LD50) using bolus intravenous injections in white mice. The testing of a number of other classes of drugs for a similar effect has shown thus far that only the digitalis class exhibits this synergism. Surprisingly, the nonionic contrast medium, metrizamide, has been shown to have a greater synergistic effect with digitalis drugs than diatrizoate ionic media. (III.) In dog experiments under Nembutal anesthesia in which aortic flow, pulmonary artery and vein pressures, systemic arterial pressure, and EKG were monitored, left atrial pressure increases as soon as or before pulmonary artery pressure rises, even at low doses of ionic contrast media administered intravenously. This may indicate 1) flow to the left heart increases dramatically, or 2) there is a very early myocardial depression. The significance of the above findings and application to clinical practice will be discussed.