Chronic cocaine administration has been associated with sensitization (an increase in drug effect) rather than the tolerance observed with many psychotropic compounds. Because cocaine acts at the presynaptic dopamine transporter, we evaluated sensitization and striatal dopamine transporter binding in vivo in several mouse strains. All strains of mice evaluated showed increased activity after cocaine compared with after saline injections. BALB/cByJ, DBA/2J, B6AF1/J and C57BL6/J mice exhibited sensitization when assayed 72 hr after five daily injections of cocaine at 20 and 40 mg/kg/day, whereas B6AF1/J mice showed sensitization at 20 but not at 40 mg/kg/day. CD-1 mice did not exhibit sensitization at either dose. Striatal dopamine transporter binding in vivo was increased in DBA/2J and B6AF1/J mice when determined 72 hr after five injections of 40 mg/kg/day cocaine. In contrast, a continuous infusion of cocaine at the same dose and duration did not produce sensitization or binding changes in DBA/2J mice. The time course of transporter binding alterations after intermittent cocaine exposure indicated no change at 1 day, increased binding at 3 days, a return to control levels at 7 days and decreased binding at 14 days. These data indicate that both sensitization and alterations in dopamine transporter binding occur after chronic cocaine injection but that these changes are unlikely to be directly related.