In 6-[18F]fluoro-L-dopa (Fdopa)/positron emission tomography (PET) studies, carbidopa pretreatment increases the Fdopa bioavailability to the brain and enhances the intensity of striatal PET images. Different PET research teams have used various carbidopa doses and routes of administration in non-human primate studies. The purpose of this study was to examine the plasma profiles of carbidopa and the effect of the route of administration of carbidopa on a Fdopa/PET scan. Cynomolgus monkeys were given carbidopa either orally (5 mg/kg), intraperitoneally (2.5 and 5 mg/kg) or intravenously (5 mg/kg) 60-90 min prior to the Fdopa injection. Carbidopa-treated monkeys were compared to monkeys without carbidopa treatment. No carbidopa was detected in the plasma samples when it was given orally, possibly due to poor absorption in the gastrointestinal tract. In addition, the striatal and cortical activities were not statistically different from those of the untreated monkeys, indicating that little or no inhibition of the peripheral decarboxylation of Fdopa by carbidopa had taken place. When carbidopa was given intraperitoneally at a dose of 2.5 and 5 mg/kg and intravenously at 5 mg/kg, plasma carbidopa concentrations at the time of Fdopa injection were 0.95 +/- 0.26, 2.22 +/- 0.23 and 2.79 +/- 0.26 micrograms/ml, respectively. Because of inhibition of peripheral decarboxylation of Fdopa by carbidopa, more Fdopa was available for transport into the brain and as a result, both the striatal and cortical activities were significantly higher than those of the untreated monkeys. Carbidopa administration had no effect on either the striatal-to-cortical activity ratio or the striatum uptake value.