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A two-group crossover design experiment was used in eight dogs to compare the effects of intrathecally injected (0.25 mL/kg, 180 mg I/mL) metrizamide and iohexol. Additional acute observations were made in four of the dogs following a high dose (0.45 mL/kg of 300 mg I/mL) of each agent. In computed tomographic observations, there was progressive passage of each contrast medium across the interface between the cerebrospinal fluid and the brain, and statistically identical levels of each contrast medium were present in the cerebral gyri. There was a similar passage of contrast medium across the interface between the cerebrospinal fluid and the spinal cord. The rate of passage of each agent into the brain parenchyma suggested their active transport rather than a simple diffusion. In both T2-weighted magnetic resonance imaging and histopathologic studies, there was no evidence of cerebral edema following either high or low doses of each agent. In T1-weighted images made following the intravenous injection of gadolinium-DTPA (0.1 mmol/kg), the blood-brain barrier was intact.