Infantile spasms most commonly show symmetric behavioral and electroencephalogram (EEG) manifestations. Asymmetric and asynchronous behavioral spasms occur occasionally, but their relationship to ictal EEG and to other localizing studies has not received much attention. We reviewed 75 consecutive video-EEG recordings, done at UCLA from 1982 to 1992, that contained infantile spasms; 8,680 spasms were scored for behavioral and EEG asymmetry and asynchrony. Of the recorded spasms, 25% were asymmetric and 7% were asynchronous. Most asymmetric of asynchronous spasms were associated with an ictal EEG discharge that was contralateral to the behaviorally more involved side. In 12 of the 60 patients (20%), more than half of the recorded spasms were asymmetric of asynchronous. Baseline EEG, magnetic resonance imaging, positron emission tomography, and neurological examination revealed structural and functional brain abnormalities that involved the contralateral central region significantly more often in the children with > 50% spasm asymmetry or asynchrony than in the other children. Partial seizures with lateralized motor behavior also occurred frequently in these children. The findings suggest that asymmetric and asynchronous spasms are generated by a cortical epileptogenic region that involves the primary sensorimotor area. The combination of asymmetric and asynchronous infantile spasms, partial motor seizures involving the same side of the body, and pathology in the contralateral central region may represent a unique subset of symptomatic localization-related infantile epilepsy.