The central nervous system (CNS) may be highly susceptible to the toxic effects of conventional contrast media (CM). The current study quantifies levels of diatrizoate in canine cerebrospinal fluid (CSF) following intravenous administration and examines how these levels change as CSF production rate is reduced. Cerebrospinal fluid was collected continuously from the cisterna magna of anesthetized dogs before and after the administration of diatrizoate (1 mL/kg bolus followed by a 12.5 microliters/kg/minute maintenance infusion, IV). The influence of CSF production rate on CSF diatrizoate levels was examined by injecting acetazolamide (30 mg/kg, IV). Diatrizoate levels in CSF were quantified by a high performance liquid chromatography (HPLC) method. Baseline CSF production was 81.5 microliters/minute and dropped to 37.4 microliters/minute following diatrizoate and to 29.5 microliters/minute following acetazolamide. The concentration of diatrizoate in CSF averaged 166 micrograms/mL and increased significantly to 379 micrograms/mL following acetazolamide with no change in serum concentration (1.3 mg/mL). These experimental results suggest that appreciable quantities of intravenously administered diatrizoate may enter the CNS, and that these quantities may increase significantly with reduced CSF production. This may help to explain CSF enhancement and certain CNS toxicity after the intravenous administration of CM.