This study examines the extent to which the auditory middle latency response (MLR) of the guinea pig is sensitive to sound localization cues such as interaural level and time differences (ILD and ITD, respectively). The MLR was recorded with an epidural electrode placed over the auditory cortex of an anesthetized guinea pig. Click stimuli were presented monaurally or binaurally with various ILDs and ITDs. The MLR was much larger for contralateral stimulation than for ipsilateral stimulation, and its amplitude was intermediate for diotic stimulation. The MLR amplitude was sensitive to both ILD and ITD: it decreased as the ipsilateral stimulus increased in level or advanced in time relative to the contralateral stimulus. The steep slope of the amplitude-versus-ITD function fell within an ITD range of +/- 330 mu s, namely the guinea pig's physiological ITD range. The response reduction that resulted from increasing the relative level of the ipsilateral level could be cancelled out by advancing the contralateral onset time relative to the ipsilateral onset time. This parallels the "time-intensity trading" in sound lateralization exhibited in human psychophysics. The results imply that the binaural interaction in the guinea pig MLR reflects aspects of neural processes that are involved in sound localization. (c) 2005 Elsevier B.V. All rights reserved.