Tomographic imaging of central nicotinic acetylcholine receptors (nAChRs) via single photon emission computed tomography (SPECT) has been hampered by the lack of a radioligand with suitable in vivo binding characteristics. Therefore, a novel analog of epibatidine, (6)-exo-2-(2-iodo-5-pyridyl)-7-azabicyclo[2.2.1]heptane (IPH), labeled with [ 125 I] or [ 123 I] was evaluated as an in vivo marker of central nicotinic acetylcholine receptors (nAChRs). [ 125 I]IPH showed substantial brain penetration (4.2% of the injected dose at 30 min) and a cerebral biodistribution in mice consistent with the in vivo labeling of nAChRs (% injected dose/gram of thalamus, superior colliculi : cerebellum). [ 125 I]IPH binding sites were shown to be saturable with unlabeled IPH (ED 50 approximately 1 ยตg/kg). The uptake of [ 125 I]IPH was blocked significantly by the nicotinic agonists, cytisine, lobeline, and (2)-nicotine, but not by the noncompetitive nAChR antagonist, mecamylamine. Antagonists of muscarinic (scopolamine), serotonin (ketanserin), and opioid (naloxone) receptors had no significant effect on [ 125 I]IPH binding. A preliminary SPECT imaging study with [ 123 I]IPH in a baboon showed [ 123 I]IPH to localize in nAChR-rich areas of brain (thalamus . frontal cortex . cerebellum). [ 123 I]IPH binding in baboon brain was also displaced (35-45% displacement) by a challenge dose of cytisine showing that a well-characterized nicotinic agonist effectively competes for [ 123 I]IPH binding sites. [ 123 I]IPH seems well suited for imaging studies of nAChRs and, to our knowledge, is the first SPECT agent that has allowed for the visualization of nAChRs in primate brain.