The present study revealed striking task-dependent differences in immediate-early gene activity in the two main subregions (granular and dysgranular) of the retrosplenial cortex. In addition, there were activity differences along the rostro-caudal axis of both subregions. Two groups of rats were trained on a working memory task in a radial-arm maze, one group in the light, the other in the dark. Each working memory group had two sets of yoked controls. Working memory consistently increased retrosplenial immediate-early gene activity (c-fos and zif268 ), although systematic differences occurred in the granular and dysgranular subregions. Both c-fos and zif268 expression increased in granular cortex irrespective of whether the spatial memory task was in the light or dark. In contrast, only in the light did spatial memory increase dysgranular cortex activation. Correlations based on the counts of Fos-positive cells helped to reinforce the particular association between the dysgranular retrosplenial cortex and radial-arm maze performance in the light. These results provide clear evidence for proposed functional differences between the major retrosplenial subregions: the granular cortex contributes to spatial learning and navigation based on both internal and external cues (light and dark), while dysgranular cortex is more selectively involved when distal visual cues control performance (light only).