Subjects with Asperger's syndrome (AS) are impaired in social interaction and imitation, but the underlying brain mechanisms are poorly understood. Because the mirror-neuron system (MNS) that matches observed and executed actions has been suggested to play an important role in imitation and in reading of other people's intentions, we assessed MNS functions in 8 adult AS subjects and in 10 healthy control subjects during imitation of still pictures of lip forms. In the control subjects, cortical activation progressed in 30 to 80-millisecond steps from the occipital cortex to the superior temporal sulcus, to the inferior parietal lobe, and to the inferior frontal lobe, and finally, 75 to 90 milliseconds later, to the primary motor cortex of both hemispheres. Similar activation sites were found in AS subjects but with slightly larger scatter. Activation of the inferior frontal lobe was delayed by 45 to 60 milliseconds and activations in the inferior frontal lobe and in the primary motor cortex were weaker than in control subjects. The observed abnormal premotor and motor processing could account for a part of imitation and social impairments in subjects with AS. Ann Neurol 2004