Five healthy male subjects participated in a classical conditioning experiment, and positron emission tomography (PET) was used to compare regional cerebral blood flow before and after conditioning. The subjects participated in three different experimental phases. In the first (habituation) phase they listened to 24 repetitions of a tone with random intervals. In the second (acquisition) phase, the tone was paired with a brief shock to the wrist. In the third (extinction) phase, the tone was presented alone again. 15OPET scans were taken during the habituation and extinction phases. Because the habituation and extinction phases were similar, any difference in blood flow to the tones presented during extinction probably reflected conditioning that occurred during the acquisition phase. Statistical parametric mapping (SPM) analysis of the PET data showed significantly increased activation in the right hemisphere in the orbito-frontal cortex, dorsolateral prefrontal cortex, inferior and superior frontal corticies, and inferior and middle temporal corticies. The only activated areas in the left hemisphere were area 19 and the superior frontal cortex. The results are interpreted as evidence for the involvement of cortical areas in human classical conditioning.