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Recent studies implicate regions in the frontal, temporal and occipital cortices of the brain in audio-visual (AV) integration of familiar objects. It remains unclear, however, which brain regions contribute to the creation of object-related AV memories, and whether activation of these regions is affected by crossmodal congruency. Here we used event-related functional MRI in a subsequent memory paradigm to investigate the neural substrates of successful encoding of semantically congruent and incongruent AV memories. Creation of both types of memories activated a region in the left inferior frontal gyrus (IFG). In addition, successful encoding of semantically related and unrelated AV pairs was correlated with increased activity in regions within the right lateral occipital cortex and bilateral lateral temporal cortex, respectively. These results may highlight a common role of IFG in retrieval of semantic information during encoding and suggest that the occipital and temporal cortices differentially process perceptual versus conceptual associations of AV memories.