Amplitude-integrated electroencephalography monitors different aspects of cerebral function in neonatal intensive care units. To examine the influence of various antiepileptic drugs on the background patterns and voltage of amplitude-integrated electroencephalography recordings, we screened 191 tracing segments originating from 77 newborns treated with antiepileptic drugs. The influences of lorazepam, diazepam, and phenobarbital given as bolus doses, and midazolam and lidocaine given in continuous infusion, were examined. Voltages and patterns before and after drug administration were assessed. Time taken to return to previous voltage was assessed in clinically significant cases. Chi-square and Wilcoxon tests were used for statistical analyses. Significant changes were evident after lorazepam, diazepam, phenobarbital, and midazolam administration. Depending on the voltage-assessment method, a clinically significant depression of the lower voltage border occurred in 25-35% of tracings, and of the upper border in 16-32%. In 12% of tracings, change to a worse pattern was noted. The average time for recovery to predrug administration voltage was 2.5 hours (range, 15 minutes to 15 hours). Changes in amplitude-integrated electroencephalography tracings occur after antiepileptic drugs are infused. These changes include deterioration of pattern and depression of voltage that may persist for a considerable period. The potential depressing effects of these drugs should be taken into consideration when assessing amplitude-integrated electroencephalogram tracings.