Previous picture-word interference (PWI) fMRI-paradigms revealed ambiguous mechanisms underlying facilitation and inhibition in healthy subjects. Lexical distractors revealed increased (enhancement) or decreased (suppression) activation in language and monitoring/control areas. Performing a secondary examination and data analysis, we aimed to illuminate the relation between behavioral and neural interference effects comparing target-related distractors (REL) with unrelated distractors (UNREL). We hypothesized that interference involves both (A) suppression due to priming and (B) enhancement due to simultaneous distractor and target processing. Comparisons to UNREL should remain distractor unspecific even at a low threshold. (C) Distractor types with common characteristics should reveal overlapping brain areas. In a 3T MRI scanner, participants were asked to name pictures while auditory words were presented (stimulus onset asynchrony [SOA] = -200 msec). Associatively and phonologically related distractors speeded responses (facilitation), while categorically related distractors slowed them down (inhibition) compared to UNREL. As a result, (A) reduced brain activations indeed resembled previously reported patterns of neural priming. Each target-related distractor yielded suppressions at least in areas associated with vision and conflict/competition monitoring (anterior cingulate cortex [ACC]), revealing least priming for inhibitors. (B) Enhancements concerned language-related but distractor-unspecific regions. (C) Some wider brain regions were commonly suppressed for combinations of distractor types. Overlapping areas associated with conceptual priming were found for facilitatory distractors (inferior frontal gyri), and areas related to phonetic/articulatory processing (precentral gyri and left parietal operculum/insula) for distractors sharing feature overlap. Each distractor with semantic relatedness revealed nonoverlapping suppressions in lexical-phonological areas (superior temporal regions). To conclude, interference combines suppression of areas well known from neural priming and enhancement of language-related areas caused by dual activation from target and distractor. Differences between interference and priming need to be taken into account. The present interference paradigm has the potential to reveal the functioning of word-processing stages, cognitive control, and responsiveness to priming at the same time. © 2012 The Authors.