Angina pectoris is a common symptom and one that can have profound implications for the patient. However, it correlates poorly with the extent of myocardial ischaemia and with prognosis. In order to understand more fully the heterogeneity of the experience of chest pain, we have adopted the technique of functional neuroimaging, where positron emission tomography is used to measure regional cerebral blood flow as an index of regional neuronal activation, during myocardial ischaemia in patients with coronary artery disease. We have been able to delineate those brain areas that are involved in the perception of angina: the hypothalamus, periaquaductal grey, thalami and bilaterally the prefrontal cortex and in the left the inferior anterocaudal cingulate cortex. By studying patients with silent myocardial ischaemia, we have established that the silence is not merely a matter of impaired afferent signalling resulting from autonomic neuropathy, but that it is associated with a failure of transmission of signals from the thalamus to the frontal cortex. At the other end of the spectrum, we have studied patients with syndrome X, a condition of chest pain with ischaemic-like stress electrocardiography (ECG) but entirely normal coronary angiogram; (on the basis of our own and other data we consider an ischaemic aetiology to be most unlikely in this condition). In syndrome X, distinct patterns of cerebral activation were found with characteristic activation of the right anterior insula at its junction with the frontal operculum. In conclusion, we present a unified view of the cerebral handling of afferent signals from the heart throughout this spectrum of experience of chest pain, a view that accounts for the clinical features of the patients studied.