It is now reasonably well established that Helicobacter pylori is the most likely cause for duodenal ulcer. What is not clear is how this infection is related to the excess acid production, why few people with Helicobacter pylori infection have duodenal ulcer and how diet is related to duodenal ulcer. Here it is suggested that a deficiency of cis-unsaturated fatty acids (otherwise called as polyunsaturated fatty acids, PUFAs) especially gamma-linolenic acid, dihomo-gamma-linolenic acid, arachidonic acid and eicosapentaenoic acid may be responsible for duodenal ulcer. Patients with active duodenal ulcer are known to have low concentrations of these PUFAs in their plasma phospholipid fraction and they revert to normal levels after treatment with H2 blockers. In addition, these PUFAs have the ability to inhibit the growth of Helicobacter pylori, suppress acid production and both in experimental animals and humans these PUFAs could heal the ulcer and protect the gastric mucosa from aspirin and steroid-induced damage. Further, PUFAs have other beneficial actions such as capacity to prevent/arrest atherosclerosis, lower plasma cholesterol and triglyceride levels and cytotoxic action on tumour cells. Since PUFAs can be administered over long periods of time and are relatively non-toxic, it is suggested that PUFAs may be exploited as potential anti-ulcer agents.