Plasma concentration measurements have confirmed that the advantageous hepatic metabolism of esomeprazole results in a greater delivery of acid suppressant to the systemic circulation, compared with an equal dose of omeprazole. Also, this superior delivery has been shown to cause a more consistent and greater suppression of pentagastrin-stimulated gastric acid secretion by esomeprazole, 20 mg, compared with omeprazole, 20 mg. The superior acid-suppressant properties of esomeprazole have been revealed by extensive 24-h intragastric pH-monitoring studies. Compared with omeprazole, 20 mg, esomeprazole, 20 mg and 40 mg, has been shown to give superior outcomes on three key measures of antisecretory effect: (1) consistency amongst individuals; (2) duration over the 24-h cycle; (3) overall impact on pH. As there is a substantial increment of acid control from esomeprazole, 20 mg, to esomeprazole, 40 mg, this latter dose is the most appropriate to investigate for modern initial therapy of reflux disease, with the aim of achieving the highest possible response rates in the shortest possible time.