Robust perception of self-motion requires integration of visual motion signals with non-visual cues. Neurons in area MSTd may be involved in this sensory integration, as they respond selectively to global patterns of optic flow, as well as translational motion in darkness. Using a virtual reality system, we have characterized the three-dimensional (3D) tuning of MSTd neurons to heading directions defined by optic flow alone, inertial motion alone, and congruent combinations of the two cues. Among 255 MSTd neurons, 98% exhibited significant 3D heading tuning in response to optic flow, whereas 64% were selective for heading defined by inertial motion. Heading preferences for visual and inertial motion could be aligned, but were just as frequently opposite. Moreover, heading selectivity in response to congruent visual/vestibular stimulation was typically weaker than that obtained using optic flow alone, and heading preferences under congruent stimulation were dominated by the visual input. Thus, MSTd neurons did not integrate visual and non-visual cues to achieve better heading selectivity. A simple two-layer neural network, which received eye-centered visual inputs and head-centered vestibular inputs, reproduced the major features of the MSTd data. The network was trained to compute heading in a head-centered reference frame under all stimulus conditions, such that it performed a selective reference frame transformation of visual, but not vestibular, signals. The similarity between network hidden units and MSTd neurons suggests that MSTd is an early stage of sensory convergence involved in transforming optic flow information into a (head-centered) reference frame that facilitates integration with vestibular signals.