Epileptic seizures are reported to occur frequently in Rett syndrome (RS). We evaluated the hypothesis that many events classified as seizures in RS represent other paroxysmal, non-epileptic events; thus, the overall incidence of seizures in RS is overestimated. We conducted video/polygraphic/EEG monitoring sessions (8-120 h duration) in 82 RS females (ages 2-30 years). Fifty-five patients (67%) had a history of seizures and 43 (52%) were receiving anticonvulsants. All had abnormal EEGs. These abnormalities included epileptiform findings, the frequency of which ranged from 60% of patients in clinical stage IV to 97% of patients in clinical stage III. During monitoring, electrographic seizures were recorded in only 13 patients (16%) and included both partial and generalized events. Clinical events correlating with EEG seizure discharges were identified by parents during only 5 of these recordings. The parents of 23 (42%) of the 55 patients with a history of seizures identified events during monitoring that they felt were representative of the child's typical 'seizures', but which were not associated with EEG seizure discharges. These 'non-seizure' events included episodes of motor activity, such as twitching, jerking, head turning, falling forward, and trembling, as well as episodes of staring, laughing, pupil dilatation, breath holding and hyperventilation. These studies confirm that the occurrence of epileptic seizures is overestimated in RS, and further suggest that actual seizures may be under-recognized. Video/EEG monitoring can provide definitive information regarding the need for anticonvulsant therapy in RS.