Since the high-affinity state of dopamine D2 receptors may be abnormal in psychomotor diseases, it is desirable to develop a radioactive agonist to label this high-affinity site for possible clinical diagnostic use. (+)PHNO is a selective D2 agonist used to treat Parkinson's disease. We prepared L3H1( + )PHNO from allyl-des-propyl-(+)PHNO. In binding to dopamine receptors in homogenates of canine brain striata, L3H]( +)PHNO had a dissociation constant of 0.35 nM in the absence of NaC1, and 0.56 nM in the presence of NaC1. Dopamine agonists and antagonists inhibited the binding of r3H]( + )PHNO at drug concentrations similar to those inhibiting other [3H]ligands at D2 receptors, but not similar to those acting at D4 receptors. Approximately 90% of the total 3HPHNO binding was specific. Guanilylimidodiphosphate markedly inhibited 3HPHNO binding, suggesting that r3H]( +)PHNO was binding primarily to the highaffinity state of dopamine D2 receptors rather than to D3 receptors. The density of the L3H]( + )PHNO binding sites was equal to that of L3H1emonapride (or [3H]YM-09151-2), both densities of which were 1.5-to 2-fold higher than that of [3H]spiperone, compatible with the idea that 3HPHNO binds to monomers of D2, while [3H]spiperone binds to dimers of D2. Although 13H](+)PHN0 has good selectivity and affinity for the highaffinity state of D2, the 13H]ligand was sensitive to endogenous dopamine, since washing the tissue lowered the dissociation constant. For future in vivo labelling of D2 by an agonist, therefore, it will be essential to search for a related 13H]ligand with an even lower dissociation constant. o 1993 Wiley-Liss, Inc