Hemispheric language dominance, as determined by intracarotid amobarbital sodium injections, and handedness, as reflected by writing and drawing preference, were evaluated in a select group of patients with intractable seizures who had documented focal epilepsy originating from one temporal lobe. Of the patients with left temporal lobe seizure focus, an unusually high percentage of right-handed patients (4/26 [15%]) had right hemisphere language dominance. Pathologic findings of the resected temporal lobe in these patients revealed microscopic damage (hippocampal sclerosis) of the hippocampus in three of three cases; one patient also had a small hamartoma in the midtemporal gyrus. We hypothesize that crossed dominance resulted from disruption by epileptiform activity during early development of selective areas of the left hemisphere.