Although modern medicine therapy reliably heals peptic ulcers, relapse is the rule and remains a major challenge to investigators and practitioners alike. Several factors associated with ulcer recurrence have been identified but pathogenetic mechanisms are obscure. Some recent studies suggest that the type of treatment used to heal the initial ulcer influences the propensity to recurrence. Although there is circumstantial evidence that relapse may be accelerated after initial treatment with H2-receptor antagonists, overall it appears that differences in recurrence rates are more likely due to the influence of colloidal bismuth subcitrate in reducing recurrence rates. Several mucosal abnormalities have been identified in patients with peptic ulcer disease in remission. These include defective gastric mucus, reduced duodenal bicarbonate secretion and altered synthesis of certain prostaglandins, particularly of the E series. Decreased salivary secretion of epidermal growth factor and gastric Campylobacter pylori infections have also received much attention recently. It is postulated that the cause of recurrent ulceration, like that of initial ulceration, is multifactorial, and that local factors caused by the initial ulcer may contribute to the propensity of recurrence.