Event-related brain potentials to non-attended auditory stimuli were recorded from patients with dorsolateral prefrontal cortex (DPFCx) lesions and from age-matched control subjects as they performed a visual reaction time task. Auditory stimuli consisted of monaural sequences of repetitive standard tones (1000 Hz) and occasional deviant tones of a higher frequency (1300 Hz). In comparison with control subjects, DPFCx patients showed enhanced P1 amplitudes (mean peak latency 50 msec), consistent with reduced frontally mediated gating of sensory input to the auditory cortex. The mismatch negativity (MMN) elicited by deviant tones was reduced in DPFCx patients over a broad latency range (130-210 msec), especially over the lesioned hemisphere and for tones delivered to the ear ipsilateral to the lesion. The results suggest that DPFCx and DPFCx-temporal projections play a critical role in involuntary orienting to physical changes in sequences of non-attended auditory stimuli.