In this study, we investigated whether the left and right hemispheres are differentially involved in causal inference generation. Participants read short inference-promoting texts that described either familiar or less-familiar scenarios. After each text, they performed a lexical decision on a letter string (which sometimes constituted an inference-related word) presented directly to the left or right hemisphere. Response-time results indicated that hemisphere of direct presentation interacted with type of inference scenario. When test stimuli were presented directly to the left hemisphere, lexical decisions were facilitated following familiar but not following less-familiar inference scenarios, whereas when test stimuli were presented directly to the right hemisphere, facilitation was observed in both familiar and less-familiar conditions. Thus, inferences may be generated in different ways depending on which of two dissociable neural subsystems underlies the activation of background information.