Although it has been consistently shown that readers generate bridging inferences during story comprehension, little is currently known about the neural substrates involved when people generate inferences and how these substrates shift with factors that facilitate or impede inferences, such as whether inferences are highly predictable or unpredictable. In the current study, functional magnetic resonance imaging (fMRI) signal increased for highly predictable inferences (relative to events that were previously explicitly stated) bilaterally in both the superior temporal gyri and the inferior frontal gyri. Interestingly, high working memory capacity comprehenders, who are most likely to generate inferences during story comprehension, showed greater signal increases than did low working memory capacity comprehenders in the right superior temporal gyrus and right inferior frontal gyrus. When comprehenders needed to draw unpredictable inferences in a story, fMRI signal increased relative to explicitly stated events in the left inferior gyrus and in the middle frontal gyrus, irrespective of working memory capacity. These results suggest that the predictability of a text (i.e., the causal constraint) and the working memory capacity of the comprehender influence the different neural substrates involved during the generation of bridging inferences.