The present study reports the ion dependency of 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)[3H]tropane ([3H]CFT) binding to the dopamine transporter in the rat striatum. The results indicate that [3H]CFT binding to synaptosomal P2 membranes requires low concentrations of Na+ (peak binding between 20 and 50 mM Na+), is stimulated by phosphate anion or I-, but is unaffected or only slightly affected by F-, Cl-, Br-, NO3-, or SO(4)2-. Concentrations of Na+ of > 50 mM become inhibitory except in the presence of I-, which shifts peak binding levels toward higher Na+ concentrations and also elevates the peak binding level. K+ strongly decreased [3H]CFT binding with a shallow inhibition curve, and Na+ could not overcome this effect. Saturation analysis of [3H]CFT binding revealed a single binding site changing its affinity for CFT depending on the concentration of sodium phosphate buffer (6, 10, 30, 50, 130, or 200 mM; 1 mM plus 49 mM NaCl versus 10 mM plus 40 mM NaCl; or 1 mM plus 129 mM NaI versus 10 mM plus 120 mM NaI). No differences were observed in the density of CFT binding sites between any of the conditions examined.