This study was undertaken to assess a new method for the non- invasive determination of regional cerebral blood flow without the use of radioactive tracers. Specifically, we investigated a new 19F NMR technique that has been used to measure the clearance of a fluorinated inert gas, CHF3 from the cerebral cortex of the cat. The 19F NMR technique was tested in three ways. First, the C02- dependence of the measured cortical blood flows was investigated. Second, the cortical blood flow values calculated by 19F NMR were compared with cortical blood flow values determined simultaneously by radioactive microsphere techniques. Finally, the effects of CHF3 on cortical cerebral blood flow, and the short-term toxic effects of CHF3, were evaluated.