One of the most important factors controlling material specific processing in the human brain is language dominance, i.e. hemispheric specialization in semantic processes. Although previous studies have shown that lateralized long-term memory processes in the medial temporal lobes are modified in subjects with atypical (right) language dominance, the effect of language dominance on the neural basis of working memory (WM) has remained unknown. Here, we used functional MRI (fMRI) to study the impact of language dominance on the neural representation of WM. We conducted an nback task in three different load conditions and with both verbal and nonverbal (spatial) material in matched groups of left and right language dominant subjects. This approach allowed us to investigate regions showing significant interactions between language dominance and material. Overall, right dominant subjects showed an increased inter-individual variability of WM-related activations. Verbal WM involved more pronounced activation of the left fusiform cortex in left dominant subjects and of the right inferior parietal lobule in the right dominant group. Spatial WM, on the other hand, induced activation of right hemispheric regions in left dominant subjects, but no specific activations in right dominant subjects. Taken together, these findings indicate that the neural basis of verbal WM processes depends on language dominance and is more mutable in right dominant subjects. The increased variability in right dominant subjects strongly suggests that a standard network of material-dependent WM processes exists in left dominant subjects, and that right dominant subjects use variable alternative networks. Hum Brain Mapp 30:2032Mapp 30: -2043Mapp 30: , 2009. V V C 2008 Wiley-Liss, Inc.