1. Adult male rats were implanted with chronic medial prefrontal cortex cannulae. 2. On each of 5 consecutive days, rats received bilateral 0.5 ml intra-prefrontal cortex injections of either 5 mg d-amphetamine or saline, followed by a subcutaneous injection of either 1 mg/kg d-amphetamine or saline. 3. Immediately after the drug treatments each rat was placed into a photocell equipped locomotor activity chamber for 60 min. 4. Administration of d-amphetamine into the prefrontal cortex did not block the acute locomotor response to subcutaneous d-amphetamine nor did it in itself produce an increase in locomotor activity. However, prefrontal cortex amphetamine treatments did attenuate the sensitized locomotor effects of subcutaneous amphetamine that developed over trials/days. 5. Dopamine in the prefrontal cortex may be involved in the development of amphetamine-induced behavioral sensitization.