Ionic contrast media currently used in cerebral angiography frequently cause discomfort due to hyperosmolality. This double-blind, multicenter trial compared two ionic media, meglumine iothalamate and meglumine-Na diatrizoate, with the new nonionic agent, iohexol, in 277 patients undergoing cerebral angiography. Vital signs, cardiovascular changes, and neurologic status were evaluated before, during, and after injection. Patients were observed for adverse reactions for up to 24 hours following studies. Patient discomfort and image quality were evaluated. Visualization was good or excellent with all media studied. No significant physiological differences were observed between the ionic and iohexol groups, but fewer iohexol patients experienced large increases (greater than 20 mmHg) in systolic blood pressure. Iohexol patients experienced significantly less discomfort; ionic patients reported severe discomfort 21/2 times more often. This finding was attributed to iohexol's low osmolality. Iohexol may be indicated particularly for use in selective angiograms where discomfort is a factor and for patients suspected of having blood-brain barrier disruption.