Data on handedness and speech lateralization in patients selected for amobarbital studies have frequently been extrapolated to the normal population, despite the high frequency of brain injuries which might alter lateralization in these patients. To achieve a better definition of the relationships between brain injury, handedness, and speech lateralization, we reviewed the records of 237 consecutive patients who underwent amobarbital testing. Brain injuries sufficient to cause right hemiparesis were strongly associated with left handedness and atypical (right hemisphere or bilateral) speech representation. Among nonhemiparetic patients, abnormal extratemporal radiological findings were associated with an increased incidence of left handedness and atypical speech lateralization. It was not possible to demonstrate any alteration in handedness or speech representation resulting from abnormalities restricted to the temporal lobes, although such alterations could not be excluded. Handedness and speech lateralization established using amobarbital studies in neurosurgical patients may not be representative of the normal population.