BACKGROUND/AIMS: Levosulpiride is the levo-enantiomer of sulpiride, a well-known antiemetic, antidyspeptic and antipsychotic drug. This study was undertaken to investigate the effects of levosulpiride on esophageal symptoms, esophageal peristalsis, and lower esophageal sphincter pressure (LESP), as well as evaluate the side effects in patients with nonspecific esophageal motility disorder (NEMD). METHODS: Thirty patients with NEMD (12 males and 18 females, with a mean age 48.6 +/- 13.0 years old) were administered 25 mg of levosulpiride t.i.d. for 2 weeks. Symptom assessment, esophageal manometry, blood biochemistry and serum prolactin concentrations were evaluated before and after treatment. For the evaluation of serum prolactin concentrations according to the dose of levosulpiride, 10 healthy volunteers were administered 25 mg or 12.5 mg of levosulpiride t.i.d., and serum prolactin concentrations were examined before and after treatment weekly. RESULTS: After treatment with levosulpiride, the symptom score was improved significantly (6.5 +/- 3.0 vs. 3.9 +/- 2.7, p < 0.05), but esophageal manometric findings were not improved. Two patients developed breast engorgement and the serum prolactin concentration was significantly elevated after treatment with levosulpiride. However, the increased serum prolactin level returned to a normal level within one week, and there was no difference in regards to the dose of levosulpiride. CONCLUSIONS: Levosulpiride did not improve the esophageal motor abnormality, but was effective for esophageal symptoms, which might be the result of the antidopaminergic effect on the central nervous system. Hyperprolactinemia developed in all patients, but it was normalized within a week, and symptoms for hyperprolactinemia were seen in only a few cases.