Nefopam is a nonnarcotic analgesic drug with some antidepressant properties. Pigs were used to study the regional distribution and kinetics of radiolabeled nefopam in the brain using positron emission tomography (PET) scanning. First, 550–860 MBq of 11Cnefopam was administered intravenously; arterial blood samples were drawn at intervals thereafter. A Siemens Model HR 961 scanner equipped with an ECAT computer package was used for positron emission tomography scanning and for reconstructing the pig brain image. 11Cnefopam was found to cross the blood–brain barrier and enter the pig brain readily. Plasma curves showed that 11Cnefopam may be metabolized rapidly in body tissues. Differences in the time course of 11Cnefopam-derived radioactivity in pig brain regions suggest that the drug may be binding to serotonin uptake sites, as well as other receptors. However, displacement studies using a potent and selective 5-HT uptake inhibitor failed to provide conclusive proof that nefopam interacts selectively with the cerebral 5-HT transporter.