Relationships between peptic ulcer and physical activity have as yet received little attention. The prevalence of ulceration is high in racehorses and sled dogs, particularly during periods of competition. In humans, some occupational comparisons show an increased risk among manual workers, but it remains difficult to separate effects of work-related activity from social class and attendant influences of smoking, excessive alcohol consumption, shift work, and other stressors. Two studies of leisure activity point to some benefit from moderate physical activity, one finding a reduced risk of gastric ulcers and the other finding no effect on gastric ulcers but a reduced risk of duodenal ulcers in men only. Moderate physical activity could have a favorable impact on a number of risk factors for peptic ulceration. It could reduce gastric secretions and enhance immune function, with the latter reducing the risk of Helicobacter pylori infection. Moderate activity might also reduce anxiety and encourage the adoption of a healthy lifestyle, with avoidance of smoking and an excessive consumption of alcohol. However, prolonged endurance exercise seems likely to have a negative impact, suppressing immune function, reducing mucosal blood flow, and calling for frequent administration of non-steroidal anti-inflammatory drugs (NSAIDs). As with other aspects of exercise medicine, there may be a J-shaped relationship between dose and response. Limited human observations suggest a favourable response to bouts of moderate leisure activity but little benefit from heavy occupational activity and, in some animal studies, negative effects at high volumes and intensities of exercise. Further research is recommended to confirm the nature of this relationship, clarify the location of any nadir of risk for various classes of individual, and to explore mechanisms and antidotes.