Carfentanil is a potent, synthetic opiate that binds to mu opiate receptors with very high affinity (KI = 0.051 nM, 37 degrees C). In rat brain, carfentanil is 90 and 250 times more selective for mu opiate receptors compared with delta and kappa opiate receptors, respectively. Carbon-11-carfentanil was synthesized by reacting [11C]methyliodide with the carboxylic acid precursor of carfentanil. Carbon-11-carfentanil was injected intravenously in man and a baboon and the distribution of the radioactivity in the brain was monitored using positron emission tomography. High concentrations of radioactivity were observed in the basal ganglia and thalamus, intermediate concentrations in the frontal and parietal cerebral cortex, and low concentrations in the cerebellum and occipital cortex; this distribution corresponds to the known regional density of opiate receptors measured using in vitro techniques. This heterogeneous distribution could be abolished by pretreatment with naloxone (1 mg/kg), an opiate antagonist. The percent inhibition of binding by naloxone is approximately 90% in the caudate nucleus and medial thalamus for the period 30-60 min after injection; therefore, this method is associated with a high level of specific binding to opiate receptors compared with nonspecific binding sites. The ability to measure opiate receptors in vivo in man makes it possible to study a variety of neurologic and psychiatric disorders in which opiate receptors are thought to be abnormal and to study physiologic role of opiate receptors in the central nervous system.