An in vitro study was undertaken to determine the effect of diatrizoate meglumine (DM) on the resting tone of the basilar artery in rats. Isolated basilar arteries were mounted in a myograph designed to measure even very small changes in basal force development or relaxation. To standardize resting tone between different preparations, the arteries were partially activated with excess K+. DM produced a dose-dependent relaxation of partially activated cerebral arteries beginning at 6 μg/ml. The relaxation produced by low concentrations of DM (6 to 10 μg/ml) occurred before any measurable increase in osmotic pressure, which was shown to relax basilar artery, demonstrating a direct effect of DM on reducing tone. Higher doses (>30 μg/ml) increased osmotic pressure to a level that reduced tone when osmotic pressure was elevated to equivalent levels with sucrose. Lumbar punctures performed immediately after cerebral angiography in four patients without pathological alterations of the blood-brain barrier demonstrated concentrations of DM in the cerebrospinal fluid (CSF) of 3 to 10 μg/ml. Further analysis of the kinetics of this contrast agent indicates that it enters the CSF very rapidly after its intracarotid injection and that its continued presence is detectable in the CSF for up to 60 minutes. These data suggest that the net effect of intra-arterially injected contrast agent may include an immediate cerebral arterial dilation as a result of both the chemical nature of the agent and hyperosmolarity and that sustained dilation of cerebral arteries may last for up to an hour because of the presence of the contrast agent in the CSF. Finally, in a separate experiment the DM immediately relaxed basilar arteries constricted by hemorrhagic CSF obtained from a patient after aneurysmal subarachnoid hemorrhage.