We report the pattern of metabolic activation of the brain associated with speech, using 15O positron emission tomography (PET) in normal volunteers, as well as patients with or without language deficit. 15 trials were performed on 13 subjects. Regional oxygen metabolism with the subjects at rest was compared to that during a speech-from-memory task. As expected, there was strong activation of Broca's area and the medial left temporal lobe, corresponding to the motor speech and memory aspects of the task. In addition, both cerebellar hemispheres and pre-motor areas, as well as the right frontal operculum, supplementary motor area and right parietal lobe were active. This technique provided insight into the mechanism of aphasia in two subjects, even in one whose traditional language areas were structurally and metabolically intact at rest. We conclude that this practical activation technique may be useful not only in studying the physiology of normal brain, but also in understanding functional responses to disease.