ABSTRACT.Forty-three cases out of 10,173 consecutive EEG studies in our laboratory were identified with midline spikes (MS). These cases were then compared with 107 additional cases collected from the neurological literature. Multichannel recordings which increase the sampling time over the midline are important in the recognition of MS. Mapping montages, utilizing orthogonal chains of differential derivations, are useful in localizing the epileptiform activity. MS are highly potentially epileptogenic; 93% of our patients and 88% of the reported cases are associated with definite seizure disorders. A multitude of seizure-types are seen including generalized tonic and tonic-clonic, partial motor, complex partial,“atypical absences,”akinetic, and myoclonic. Generalized tonic-clonic is the most common seizure type (42%). It is important that midline epileptiform activity be differentiated from physiologic waveforms of sleep, especially in children. Although MS can be seen at any age from the neonate to the elderly, they are more common in children (approximately 74%). A wide range of etiologies is possible including stroke, tumor, trauma, meningoencephalitis, and congenital abnormalities. Sleep is a potent activator of MS. The neurologic exam and CT scan are abnormal in about 1/3 of patients. The most common spike location along the midline is near the Cz electrode. Additional epileptic foci are often present outside the midline but do not appear to have any significant impact on the clinical picture. An interesting finding is the tendency of partial motor seizures to secondarily generalize while complex partial seizures and other“staring”spells appear less likely to generalize.