The present study uses event-related potentials to investigate the role of prediction in the processing of information structure, a domain of language that belongs to the level of the discourse. Twenty-three native speakers of English read short contexts including three Noun Phrases (NPs) (e.g., Either an adviser or an agent can be helpful to a banker), followed by a wh-question that established the discourse role of each referent (In your opinion, which of the two should a banker hire?). The NP that the question was about (banker) was the Topic, and the two NPs that could fill the slot opened by the wh-question (adviser, agent) were the Focus NPs. The participants’ brain activity was recorded with EEG while they read the responses to the wh-questions, which differed along two dimensions: (1) the availability of the it-cleft construction (In my opinion, it is an agent…), a Focus-devoted device that makes Focus assignment predictable in the response; and (2) the discourse role of the target noun (Focus, Topic), which corresponds to the first referent in the response (In my opinion, it is an agent/a banker…). Crucially, we manipulated the phonological properties of the Focus and Topic nouns such that, if the Topic noun began with a consonant (e.g., a banker), both nouns that could fill the slot opened by the wh-question began with a vowel (e.g., an agent, an adviser) (counterbalanced in the overall design). This allowed us to measure effects of prediction at the prenominal article, before the integration of semantic and discourse information took place. The analyses on prenominal articles revealed an N400 effect for articles that were unexpected based on the phonological properties of the Focus nouns, but only in the conditions with the it-cleft. This effect emerged between 250 and 400 ms, with a frontal bias. The analyses on the noun revealed that violations of information structure (i.e., cases where the it-cleft was followed by the Topic noun) yielded a broadly distributed P600 effect, relative to appropriately clefted (i.e., focused) nouns. A similar (but numerically less robust) effect emerged for Topic relative to Focus NPs in the conditions without the it-cleft, suggesting that, in the absence of a constraining cue, comprehenders still assigned Focus to the first referent in the response. Overall, these results suggest that, when reading answers to wh-questions, comprehenders use information structure constraints (i.e., prior context + the it-cleft) to anticipate the form that the response should take (i.e., how information should be packaged). •Comprehenders use cleft constructions predictively for Focus assignment.•Effects of prediction emerged on articles preceding focused nouns.•Information structure violations yielded a P600.•Clefted nouns showed a positive brain response related to information delivery.