Positron emission tomography (PET) studies performed with [11C]raclopride have consistently reported lower binding to D2/3 receptors and lower amphetamine-induced dopamine (DA) release in cocaine abusers relative to healthy controls. A limitation of these studies that were performed with D2/3 antagonist radiotracers such as [11C]raclopride is the failure to provide information that is specific to D2/3 receptors configured in a state of high affinity for the agonists (i.e., D2/3 receptors coupled to G-proteins, D2/3 HIGH). As the endogenous agonist DA binds with preference to D2/3 HIGH relative to D2/3 LOW receptors (i.e., D2/3 receptors uncoupled to G-proteins) it is critical to understand the in vivo status of D2/3 HIGH receptors in cocaine dependence. Thus, we measured the available fraction of D2/3HIGH receptors in 10 recently abstinent cocaine abusers (CD) and matched healthy controls (HC) with the D2/3 antagonist and agonist PET radiotracers [11C]raclopride and [11C]NPA. Methods:[11C]raclopride and [11C]NPA binding potential (BP) (BPND) in the striatum were measured with kinetic analysis using the arterial input function. The available fraction of D2/3 HIGH receptors, i.e., % RHIGH available = D2/3 HIGH/(D2/3 HIGH + D2/3 LOW) was then computed as the ratio of [11C]NPA BPND/[11C]raclopride BPND. Results:No differences in striatal [11C]NPA BPND (HC = 1.00 ± 0.17; CD = 0.97 ± 0.17, P = 0.67) or available % RHIGH (HC = 39% ± 5%; CD = 41% ± 5%, P = 0.50) was observed between cocaine abusers and matched controls. Conclusions: The results of this [11C]NPA PET study do not support alterations in D2/3 HIGH binding in the striatum in cocaine dependence. Synapse, 2011. © 2011 Wiley-Liss, Inc.