Changes in limbic brain activity in response to novel configurations of visual stimuli were assessed by quantifying two immediate-early genes, c-fos and zif268. Rats were first trained to use distal, visual cues to support radial-arm maze performance. Two separate sets of visual cues were used, one in the morning (Set A) and the other in the afternoon (Set B). On the final day the experimental group was tested with a novel configuration created by combining four of the eight visual cues from Set A with four of the eight visual cues from Set B. Although each individual cue was in a familiar location, the combination of cues was novel. Comparisons with a control group revealed discrete decreases in Fos centred in the hippocampus and retrosplenial cortex. The hippocampal c-fos findings produced a dissociation with the perirhinal cortex, where no change was observed. Other regions seemingly unaffected by the novel stimulus configuration included the postrhinal, entorhinal and parietal cortices. Zif268 levels in the experimental group increased in the anterior ventral thalamic nucleus. Although previous studies have shown how the rat hippocampus is involved in responding to the spatial rearrangement of visual stimuli, the present study examined temporal rearrangement. The selective immediate-early gene changes in the hippocampus and two closely related sites (retrosplenial cortex and anterior ventral thalamic nucleus) when processing the new stimulus configuration support the notion that the hippocampus is important for learning the 'relational' or 'structural' features of arrays of elements, be they spatial or temporal.