The present study investigated the effects of repeated administration of the dopamine reuptake inhibitors N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine (BTCP) and cocaine on locomotor activity, as well as their ability to induce or express cross-sensitization. Male mice were injected with a fixed dose of BTCP or cocaine (10,20 or 40 mg/kg i.p.) for 3 consecutive days and challenged on the 4th day with one of several doses of BTCP and/or cocaine. After every daily treatment, locomotor activity was assessed. Repeated administration of cocaine produced sensitization to the locomotor activity produced by different challenge doses of both cocaine (2.5-56.6 mg/kg i.p.) and BTCP (2.5-80 mg/kg, i.p.) on day 4. Repeated administration of low and intermediate doses of BTCP did not significantly affect the locomotor activity produced by different challenge doses of BTCP, whereas tolerance-like effects were observed after the higher dose, 40 mg/kg, particularly during the 3-day regimen. Repeated administration of BTCP dose-dependently produced leftward and downward shifts of the cocaine dose-response curve. The results indicate that, under identical treatment conditions, cocaine and BTCP differ markedly with respect to their ability to cause sensitization, but differ less in terms of their ability to elicit locomotor activity in sensitized animals. The demonstration of cross-sensitization between BTCP and cocaine provides evidence for a shared mechanism of action; however, the present results also suggest that the chronic effects of cocaine and BTCP are not identical.