Neurons in the superior colliculus (SC), a prominent midbrain structure, are able to synthesize information from different senses. This synthesis plays an important role in determining whether SC-mediated orientation behaviors will be initiated. In some circumstances, multisensory integration in the SC is evident as a response that is significantly enhanced above that evoked by the most effective single-modality stimulus. It can sometimes even exceed the arithmetic sum of the single-modality responses. In other circumstances, multisensory integration is evident as response depression, an effect sometimes powerful enough to eliminate even robust single-modality responses. The conditions that produce multisensory enhancement also increase the probability of orientation responses, and those that produce multisensory response depression decrease the probability of orientation responses. Although one might posit that the capability to integrate cross-modal cues (and, in this case, alter overt behavior) would be evident in all neurons capable of responding to stimuli from two or more sensory modalities, this turns out to be incorrect. When descending influences from the cortex are temporarily inactivated, SC neurons are rendered unable to synthesize their multiple sensory inputs, and animals no longer show enhanced orientation responses. Nevertheless, the ability to respond to cues from multiple sensory modalities is retained at both the single neuron and behavioral levels. Two cortical areas have been implicated in controlling these midbrain processes: the anterior ectosylvian sulcus and the rostral lateral suprasylvian sulcus.