Narp (neuronal activity regulated pentraxin) is a secreted immediate early gene product that is induced by synaptic activity. Recent studies have indicated that Narp may be an extracellular aggregating factor for AMPA receptors. Immunohistochemical studies have revealed prominent expression of Narp in the mossy fiber pathway of the dentate gyrus, suggesting it may be released pre-synaptically. However, in vitro studies using recombinant Narp indicate that Narp may act when expressed by either pre- or post-synaptic elements. To help define Narp's mode of action, we have examined its localization in the habenula-interpeduncular pathway which also displays robust Narp expression. Focusing on this pathway as well as hippocampal and cortical Narp expression, we found prominent Narp staining in projection pathways and terminal fields. In contrast, Narp expression in dendrites was minimal in these neuronal populations. These findings indicate that, under physiological conditions, Narp is targeted to the synapse from pre- rather than post-synaptic elements. Our results also suggest that future studies focusing on these projection pathways that express high levels of Narp, in vivo, may help to understand the regulation and function of endogenous Narp.