Monaural BAEPs provide a sensitive measure of bilirubin neurotoxicity in both humans and the jaundiced (jj) Gunn rat model of acute bilirubin toxicity. Abnormalities in binaural interaction have also been demonstrated (Hear Res 53:41, 1991). We examined the differential sensitivity of monaural brainstem auditory evoked potentials (BAEPs) and evoked potential binaural difference waves (BDWs) using jj's made acutely bilirubin toxic by injecting the albumin-binding drug, sulfadimethoxine (sulfa), to displace blood bilirubin into brain tissue. Baseline 3-channel recordings (mastoid-mastoid, vertex-chin, nasion-inion) were obtained from anesthetized 17-day-old jj's. Experimental jj's were then given sulfa 100 mg/kg (n=8); control jj's were either not injected (n=4) or injected with saline (n=2). Serial BAEPs and BDWs were obtained continuously for 6h. BAEP I-II and I-III (wave II or III latency minus wave I latency), the average of monaural BAEPs from the left and right ears in the mastoid-mastoid recording montage, were compared to the latency of the positive peak of the BDW in the nasion-inion montage. Baseline values of 1.08±0.07 ms (mean±SD) for BAEP I-II, 1.97±0.21 ms for I-III, and 6.91±0.34 msec for the latency of the BDW were not significantly different between groups. In sulfa-injected animals, BAEP I-II and I-III first increased 50 min after sulfa injection versus controls(p=0.001 and p=0.002, respectively) and vs. baseline(p=0.0004 and p=0.003). BDW latency first increased 20 min after sulfa injection compared to controls (p=0.002) and to baseline (p=0.001). These findings demonstrate that BDW latency abnormalities occur before initial BAEP abnormalities in this model of acute bilirubin toxicity and suggest that electrophysiological measures of binaural interaction in the brainstem may be an earlier indication of bilirubin's damaging effect on neuronal function than conventional BAEPs. Supported by NIH NIDCD R01 DC 00369