Dopamine (DA) in the medial prefrontal cortex (PFC) can modulate the short-term retention of information and other executive functions. The present study examined whether administration of a DA D1 agonist into the PFC could have differential effects on memory retrieval in circumstances in which memory was either excellent or poor. Separate groups of rats were trained on a delayed version of the radial maze task. On the test day, the delay between the phases was either 30 min or 12 hr. Infusions of the D1 receptor agonist SKF 81297 (0.05, 0.10, or 0.20 microg/0.5 microl) into the PFC before the test phase improved memory retrieval after a 12-hr delay but disrupted performance after a 30-min delay. These data suggest that D1 receptor activity can exert differential effects over PFC function, depending on the strength of the memory trace. When memory is decremented by an extended delay, activation of PFC DA D1 receptors by an agonist can improve cognitive function.