Objective:Research on ulcer psychosomatics has plummeted since the early 1970s, to the applause of many who argue that ulcer is simply an infectious disease. The purpose of this article is to discuss the relevance of ulcer psychogenesis in the age ofHelicobacter pylori.Methods:A critical literature review was conducted.Results:There is a substantial and methodologically sound body of prospective studies linking stress with the onset and course of peptic ulcer. Psychosocial factors can be estimated to contribute to 30% to 65% of ulcers, whether related to nonsteroidal antiinflammatory drugs,H. pylori, or neither. The observed association between stress and ulcer is accounted for, in part, by recall bias, misreported diagnoses, and confounding by low socioeconomic status (a source of stress and of ulcer risk factors, such asH. pyloriand on-the-job exertion) and by distressing medical conditions (which lead to use of nonsteroidal antiinflammatory drugs). Of the residual, true association, a substantial proportion is accounted for by mediation by health risk behaviors, such as smoking, sleeplessness, irregular meals, heavy drinking, and, again, nonsteroidal antiinflammatory drugs. The remainder results from psychophysiologic mechanisms that probably include increased duodenal acid load, the effects of hypothalamic-pituitary-adrenal axis activation on healing, altered blood flow, and impairment of gastroduodenal mucosal defenses.Conclusions:Peptic ulcer is a valuable model for understanding the interactions among psychosocial, socioeconomic, behavioral, and infectious factors in causing disease. The discovery ofH. pylorimay serve, paradoxically, as a stimulus to researchers for whom the concepts of psychology and infection are not necessarily a contradiction in terms.