The extraction of optic flow cues is fundamental for successful locomotion. During forward motion, the focus of expansion (FoE), in conjunction with knowledge of eye position, indicates the direction in which the individual is heading. Therefore, it is expected that cortical brain regions that are involved in the estimation of heading will be sensitive to this feature. To characterize cortical sensitivity to the location of the FoE or, more generally, the center of flow (CoF) during visually simulated self-motion, we carried out a functional MRI (fMRI) adaptation experiment in several human visual cortical areas that are thought to be sensitive to optic flow parameters, namely, V3A, V6, MT/V5, and MST. In each trial, two optic flow patterns were sequentially presented, with the CoF located in either the same or different positions. With an adaptation design, an area sensitive to heading direction should respond more strongly to a pair of stimuli with different CoFs than to stimuli with the same CoF. Our results show such release from adaptation in areas MT/V5 and MST, and to a lesser extent V3A, suggesting the involvement of these areas in the processing of heading direction. The effect could not be explained either by differences in local motion or by attention capture. It was not observed to a significant extent in area V6 or in control area V1. The different patterns of responses observed in MST and V6, areas that are both involved in the processing of egomotion in macaques and humans, suggest distinct roles in the processing of visual cues for self-motion.