Is gastric acid responsible for the pain in patients with essential dyspepsia? The pathogenesis of symptoms in patients with essential dyspepsia is not known. Since treatment with H2-receptor antagonists has provided symptomatic relief in some reports, we carried out the present study to investigate whether gastric acid is responsible for symptoms in these patients. Fifty patients with essential dyspepsia and 25 healthy control subjects were studied. After an overnight fast, a nasogastric tube was passed and its tip positioned in the antrum under fluoroscopic control. Normal saline or 0.1 M hydrochloric acid was infused in a randomized, double-blind fashion. Eleven (22%) patients developed pain with acid infusion, but none with normal saline (p less than 0.005). In 10 of these 11 patients, pain recurred on rechallenge with acid infusion but was promptly relieved with infusion of 1 M sodium bicarbonate. None of the healthy controls developed pain on infusion of acid or saline. These observations suggest that acid has a definite role in the pathogenesis of symptoms in some patients with essential dyspepsia, although other factors may also be important. 