Prepyloric and duodenal ulcers have some common characteristics: gastric acid secretion is increased and there is an association with blood group O. Many, therefore, have considered prepyloric ulcers to be a variety of duodenal ulcer disease. From an anatomical point of view, however, prepyloric ulcers are clearly gastric ulcers. After proximal selective vagotomy, the recurrence rate is very high, amounting to more than 30% in 5 years; this is significantly higher than the rate for duodenal ulcers. Better results are obtained in prepyloric ulcers, if vagotomy is combined with a drainage procedure. In recent years, some evidence, primarily from Scandinavia, has accumulated indicating that prepyloric ulcers are more resistant to treatment with histamine H2-receptor antagonists than duodenal ulcers or ulcers located in other parts of the stomach. In addition, the recurrence rate is particularly high in prepyloric ulcers. One must, however, consider that not only have all of these studies included relatively small numbers of patients, but also the prepyloric ulcer healing rates in other studies were similar to those observed for both duodenal ulcers and ulcers located elsewhere in the stomach. Prospective studies with large numbers of patients are, therefore, necessary before a clear-cut conclusion can be reached. There are several reasons why prepyloric ulcers could be more resistant to treatment. Impaired gastric emptying, duodeno-gastric reflux or chronic gastritis, especially in conjunction with Campylobacter pylori infection, must be considered. At present, one can only speculate on the validity of any of these hypotheses.