The function of the profuse descending innervation from the auditory cortex is largely unknown; though recent studies have demonstrated that focal stimulation of auditory cortex effects frequency tuning curves, duration tuning and other auditory parameters in the inferior colliculus. Here we demonstrate that, in an anesthetized guinea pig, non-focal deactivation of the auditory cortex alters the sensitivity of populations of neurons in the inferior colliculus (IC) to one of the major cues for the localization of sound in space, interaural level differences (ILD). Primary and secondary auditory cortical areas were inactivated by a cooling loop. The ILD functions of 46% of IC cells changed when the cortex was inactivated. In extreme cases, the ILD functions changed from monotonic to non-monotonic during cooling and vice versa. Eight percent of the cells became unresponsive after deactivation of the auditory cortex. Deactivation of the cortex has previously been shown to alter the maximum spike count of cells in the IC, the change in normalized ILD functions is shown to be separate from this effect. In some cases, the ILD function changed shape when there was no change in the maximum spike count and in other cases there was no change in the shape of the ILD function even though there was a large change in the maximum spike count. Overall, the sensitivity of the IC neural population to ILD is radically altered by the corticofugal pathway.