Orthographic distinctiveness and semantic elaboration both enhance memory. The present behavioral and functional magnetic resonance imaging (fMRI) studies examined the relationship between the influences of orthographic distinctiveness and semantic elaboration on memory, and explored whether they make independent contributions. As is typical for manipulations of processing levels, words studied during semantic encoding were better remembered than words studied during nonsemantic encoding. Notably, orthographically distinct words were better recalled and received more remember responses on recognition memory tests than orthographically common words regardless of encoding task, suggesting that orthographic distinctiveness has an additive effect to that of semantic elaboration on memory. In the fMRI study, ortho-graphic distinctiveness and semantic elaboration engaged separate networks of brain regions. Semantic elaboration modulated activity in left inferior prefrontal and lateral temporal regions. In contrast, orthographic distinctiveness modulated activity in distinct bilateral inferior prefrontal, extrastriate, and parietal regions. Orthographic distinctiveness and semantic elaboration appear to have separate behavioral and functional-anatomic contributions to memory.