In recent years, a number of studies have demonstrated an important role for functional neuroimaging in the identification of residual cognitive function in persistent vegetative state. Such studies, when successful, may be particularly useful where there is concern about the accuracy of the diagnosis and the possibility that residual cognitive function has remained undetected. Unfortunately, functional neuroimaging in persistent vegetative state is extremely complex and subject to numerous methodological, clinical and theoretical difficulties. Here, we describe the strategy used to study residual auditory and speech processing in a single patient with a clinical diagnosis of persistent vegetative state. Identical positron emission tomography studies, conducted nine months apart, revealed preserved and consistent responses in predicted regions of auditory cortex in response to intelligible speech stimuli. Moreover, a preliminary functional magnetic resonance imaging examination at the time of the second session revealed partially intact responses to semantically ambiguous stimuli, which are known to tap higher aspects of speech comprehension. In spite of the multiple logistic and procedural problems involved, these results have major clinical and theoretical implications and provide a strong basis for the systematic study of possible residual cognitive function in patients diagnosed as being in a persistent vegetative state.