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1. Previous experiments in this laboratory found that striatal [H-3]WIN 35428 binding was increased in post mortem specimens from human cocaine users (Little et al, 1993a). Although structurally similar, preliminary studies have suggested that [H-3]WIN 35428 and the related cocaine congener [I-125]RTI-55 differ in some respects pharmacologically. 2. The present experiments tested the hypothesis that striatal [I-125]RTI-55 binding would be increased, as was [H-3]WIN 35428 binding, in post mortem specimens from cocaine users compared to matched controls. 3. However, computer-generated parameters derived from saturation experiments found only trends toward increased Bmax and decreased affinity (increased K-D) in the cocaine users. The magnitude of the increases were notably smaller than the statistically significant increases previously found in high affinity [H-3]WIN 35428 binding in these same subjects. 4. Evidence from the present and earlier experiments suggests that cocaine exposure may induce conformational changes in the dopamine transporter.