Although increases in dopamine secondary to the inhibition of the dopamine transporter appear to underlie the reinforcing properties of cocaine, there is presently no model that relates the elevation of synaptic dopamine to the transporter occupancy by cocaine. We propose such a model based on positron emission tomographic (PET) measurements of the brain concentration of cocaine and the assumption of rapid equilibrium between free cocaine and cocaine bound to the dopamine transporter. A euphorigenic dose of cocaine (about 40 mg) is predicted to occupy 80-90% of the transporters, while a perceptible dose (about 5 mg) occupies about 40% of the transporters. If reuptake of dopamine is reduced in proportion to the fraction of transporters occupied by cocaine, our model indicates that synaptic dopamine rises supra-linearly with occupancy, so that 5 and 40 mg doses of cocaine give about 2- and 10-fold increases, respectively. A consequence is that a given dose of cocaine produces a similar degree of elevation of dopamine regardless of the prior level of occupation of the transporters by cocaine. This prediction is supported by recent PET/neuropsychological studies in our laboratory where dopamine transporter occupancy was measured after giving methylphenidate intravenously to volunteers; similarly intense "highs" were reported whether the initial occupancy was zero or 75-85%. It could also explain why attempts to block the psychostimulant-induced "high" by pretreating subjects with drugs that block the dopamine transporter have been unsuccessful, and why the use of methylphenidate to treat cocaine addicts led to increased cocaine consumption.