WITH THE ever-growing use of angiographic procedures, it becomes increasingly important for the radiologist to select the contrast medium of highest utility and lowest toxicity. Contrast media have been examined for their toxicity by observing the changes they cause in the permeability of the blood-brain barrier, in the electroencephalograms, in cerebral blood flow, and in gross or microscopic tissue changes, or by assessing abnormalities in the animals' neurologic status. We have previously employed a simple yet highly sensitive method of comparing angiographic contrast media by injecting them into the cerebral circulation and measuring the effect on the heart rate and the systemic vessels (3, 4). The technic was reported earlier by Lindgren and Tornell (11, 12) and by Greitz (7).More recently, two new angiographic agents have been made available, iothalamate and metrizoate. Both hold promise because of their high iodine content, low viscosity of sodium salts, and reported low toxicity (1, 10). These two newer agents and the widely used diatrizoate are quite similar in chemical structure (Fig. 1), differing only in one of their side chains. The iodine content is identical in diatrizoate and iothalamate; that of metrizoate is slightly lower than the other two. Sodium diatrizoate is marketed as Hypaque 50, and methylglucamine diatrizoate as Cardiografin 85 per cent. Hypaque M75, Hypaque M90, Renografin, and Renovist are mixtures of sodium and methylglucamine diatrizoate. Sodium iothalamate goes by the trade names of Angio-Conray and Conray 400, methylglucamine iothalamate by the name of Conray. Sodium metrizoate goes by the trade names of Isopaque and Triosil. A methylglucamine and sodium metrizoate mixture is known as Isopaque-Amin.This paper is a report of the testing of sodium iothalamate and sodium metrizoate compared with sodium diatrizoate, and the testing of methylglucamine iothalamate and methylglucamine metrizoate compared with methylglucamine diatrizoate.MethodsIn one series 50 per cent solutions of sodium diatrizoate and sodium iothalamate and 52 per cent sodium metrizoate were tested. In the other series, 58.7 per cent solutions of methylglucamine diatrizoate and iothalamate and 60 per cent methylglucamine metrizoate were tested, thereby comparing solutions of equal iodine content in each group. The sodium solutions contained 300 mg iodine, and the methylglucarnine solutions 276 mg iodine per milliliter. Metrizoate, which has a slightly lower iodine content than either diatrizoate or iothalamate (which are equal in iodine content), must be prepared in slightly higher concentrations to give equivalent radiopacity. The sodium diatrizoate employed was the unaltered commercial preparation, Hypaque 50 per cent. AngioConray for sodium iothalamate and Isopaque 75 per cent for sodium metrizoate were diluted appropriately with sterile distilled water. The methylglucamine diatrizoate was prepared by diluting Cardiografin, the methylglucamine iothalamate by diluting Conray.