Sensitization to the locomotor effects of cocaine (10 mg/kg, IP) occurred in mice following preexposure to a single high dose (40 mg/kg, IP) of the drug on the previous day. Behavioral sensitization only occurred under certain experimental conditions; that is, in mice which were injected in a novel environment (i.e., the activity boxes) on day 1 and tested in the same environment on day 2. It did not occur in mice that were fully habituated to the test apparatus on both days of the experiment or in mice that were injected in the home cage on day 1. This model is consistent with studies in rats, and offers the opportunity for further characterization of the processes underlying cocaine sensitization.