This study is the first test of the novel hypothesis that perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) marks an etiological division between stress-susceptible and stress-neutral ulcerative colitis. Subjects were 47 UC patients with known p-ANCA status (19 p-ANCA-positive, 28 p-ANCA-absent). Controls were 77 university students. Subjects and controls completed the Reciprocal Attachment Questionnaire. Subjects were categorized as avoidant/nonavoidant and anxious/nonanxious based on scores for compulsive self-reliance and compulsive care seeking, respectively. A higher prevalence of avoidant attachment was present in p-ANCA-absent (58.6%) than p-ANCA-positive subjects (22.2%, chi-square = 5.95, P < 0.02). There was no difference in the prevalence of anxious attachment between p-ANCA-absent and p-ANCA-positive subjects. There was no difference in clinical and psychiatric variables between groups. This finding provides support for a psychobiological contribution to UC in a subgroup identified by the absence of p-ANCA.