The clinical use of amplitude-integrated electroencephalography in the diagnosis of seizures in high-risk newborn infants with suspected central nervous system insult is evaluated with emphasis on silent seizures. Recordings from 93 infants with suspected central nervous system insults over a period of 7 years were retrospectively analyzed for the presence of electrical seizures and for their correlation with clinical events. Thirty infants (32%) had overt clinical seizures; 29 (97%) of these manifested clear seizure patterns in their tracings, and the remaining one infant had a suspected tracing. Eleven infants (12%) had subtle clinical seizures; of these 7 (59%) had clear electrical seizures, 3 (31%) had suspected tracing, and one had a normal tracing. Fifty-two infants (56%) had no clinical events indicative of seizures; of these 8 (15%) had clear electrical seizures, 17 (33%) had suspected tracings, and 27 (52%) had normal tracings. Electroencephalographic seizures are common in sick newborn infants. Amplitude-integrated electroencephalography can provide important information concerning their neurologic status and help to confirm or refute the presence of seizures in clinically suspected cases and detect infants with silent seizures.