Background and Aims: It has previously been demonstrated that clasp and sling fibers at the human gastroesophageal junction respond differently to acetylcholine (Ach). The present study was undertaken to investigate the differences between the physiological and pharmacological properties of the two types of muscle fiber. Methods: Recordings were made of the isometric tension of human sling and clasp fibers in response to Ach, dopamine (DA), phenylephrine (Phe), and isoprenaline (Iso). These specimens were obtained from 18 patients who were operated on for esophageal cancer. Results: Both Ach and Phe increased the tension of the two types of muscle; the values in the Ach group being 3-4-fold greater than those in the Phe group, while Iso decreased the tension of both types of muscle strip. The tension of the sling fibers was reduced by DA at lower concentration, and then increased gradually as the concentration was increased. In contrast, the tension of the clasp fibers did not obviously change when the concentration of DA was lower, but a slow elevation of tension was seen with the increase in DA concentration. Conclusions: The sensitivities and maximum responses to each agent differed between the clasp fibers and sling fibers. This suggests that the two kinds of fiber have different roles in establishing tension in the lower esophageal sphincter, with implications for the medical and surgical treatment of disorders in this region. (C) 2004 Blackwell Publishing Asia Pty Ltd.