The potent cocaine analog 2.beta.-carbomethoxy-3.beta.-(4-fluorophenyl)-tropane (CFT, also designated WIN 35,428) was tritiated and evaluated as a molecular probe for cocaine receptors in caudate putamen membranes of cynomologus monkeys. Kinetic, saturation, and competition experiments indicated that [3H]CFT, like [3H]cocaine, bound to at least two components. Association and dissociation of the radioligand at 0-4.degree. occurred in two phases; the t1/2 for dissociation of the fast and slow components was 2.5 and 23 min, respectively. Saturation analysis revealed high and low affinity binding components with affinities (Kd) of 4.7 .+-. 1.2 and 60 .+-. 12 nM (means .+-. SE) and densities (Bmax) of 50 .+-. 18 and 290 .+-. 20 pmol/g of tissue, respectively. [3H]CFT was displaced stereoselectively by the enantiomers of cocaine and by the diastereoisomers of the phenyltropane analog of cocaine. Most congeners displaced [3H]CFT fully, with shallow competition curves (nH, 0.69-0.81). In contrast, several monoamine uptake inhibitors structurally unrelated to cocaine (GBR 12909, Lu 19-005, and mazindol) displaced a maximum of about 90% specifically bound [3H]CFT, with steeper competition curves (nH, 0.89-1.3), suggesting that these drugs bind to a subpopulation of [3H]CFT-labeled sites. The rank order of potency observed in the present study is identical to the rank order of potency of binding sites labeled by [3H]cocaine: Lu 19-005 > mazindol > CFT > GBR 12909 > (-)-cocaine > bupropion > WIN 35, 140 > (+)-cocaine. Moreover, there is a high positive correlation (r, 0.99, p < 0.001) between the affinities of drugs at sites labeled by [3H]CFT and [3H]cocaine. The results show that [3H]CFT and [3H]cocaine bind to a similar spectrum of sites in monkey caudate putamen. Because of its higher affinity and slower dissociation rate, [3H]CFT appears to be a superior radioligand probe for these sites.