We have developed a method to measure task-related regional cerebral blood flow (BF) responses in an awake, trained monkey using positron emission tomography (PET) and H215O. We trained an animal with operant conditioning using only positive reinforcement to climb unassisted into a modified primate chair that was then positioned in the PET scanner. A special headholder and acrylic skull cap permitted precise placement and accurate repositioning. We measured BF qualitatively with bolus injection of H215O and 40-s scan. Each session included scans at rest interposed with scans during vibration of a forepaw. Regional responses were identified using subtraction image analysis. After global normalization, a resting image was subtracted on a pixel-by-pixel basis from a comparable image collected during vibration. The region of peak response occurred in contralateral sensorimotor cortex with a mean magnitude of 11.6% (+/- 3.2%) of the global mean value for 10 separate experiments, significantly greater than the mean qualitative BF change (0.4 +/- 3.6%; p less than 0.00001) in the same region for seven rest-rest pairs. This newly developed technique forms the basis for a wide variety of experiments.