Human memory consists of multiple forms, including priming and explicit memory. Although considerable evidence indicates that priming and explicit memory are functionally and neuroanatomically distinct, little is know about when and how these different forms of memory interact. Here, behavioral and functional magnetic resonance imaging (fMRI) methods were used to examine a novel and counterintuitive hypothesis: Priming during episodic encoding may be negatively associated with subsequent explicit memory. Using an experimental design that exploited known properties of spacing or lag effects, the magnitudes of behavioral and neural priming during a second study episode were varied and the relation between these magnitudes of priming during re-encoding and performance on a subsequent explicit memory test was examined. Results revealed that greater behavioral priming (reduced reaction times) and neural priming (reduced left inferior prefrontal brain activation) during re-encoding were associated with lower levels of subsequent explicit memory. Moreover, those subjects who demonstrated greater behavioral and neural priming effects during re-encoding following a long lag tended to demonstrate the least benefit in subsequent explicit memory due to this second study episode. These findings suggest that priming for past experiences can hinder new episodic encoding.