Brainstem autonomic nuclei integrate interoceptive inputs including pain, with descending modulation, to produce homeostatic and defence outputs. Cardiac Vagal Control is especially implicated in psychophysiological processes for both health and disease and is indexed non-invasively by heart rate variability. The study aim was to determine the nature of psychophysiological response profiles for visceral pain. Nineteen healthy subjects had electrocardiographic recordings at rest and during 10 painful oesophageal balloon distensions. Cardiac Vagal Control originating from nucleus ambiguus (CVC(NA)) was determined by polynomial filter application to the electrocardiogram inter-beat interval series. Heart rate and 'Cardiac Sympathetic Index (CSI)' were also determined. Psychological state and trait, including neuroticism and extroversion, were assessed. Subjects who increased CVC(NA) to pain were more neurotic, anxious and sensory sensitive than those who decreased CVC(NA.) Cluster analysis identified two psychophysiological groups: Group 1 (n = 11) demonstrated lower baseline CVC(NA) (P = 0.0001), higher heart rate (P = 0.02) and CSI (P = 0.015), pain tolerance at lower balloon volumes (P = 0.04), but attenuated heart rate response to pain (P = 0.01). Group 2 (n = 8) had the converse profile. Neuroticism scores were higher (P = 0.0004) and extroversion lower (P = 0.01) for group 1 than group 2. Two distinct psychophysiological response profiles to visceral pain exist that are influenced by personality. These may reflect different psychobiological bases for active and passive defence repertoires. Prevalence and clinical relevance of these endophenotypes as vulnerability factors for pain and emotion disorders warrant further exploration.