Among somatoform disorders, pain disorder (DSM IV) appears to be relatively common in general practice and to cause social, psychological, and functional impairment. A previous study conducted by Lemoine (1997) has shown that sulpiride is more effective than placebo in reducing intensity and frequency of pain in this disorder. The aim of our study was to assess safety and efficacy of sulpiride in a large sample of patients under natural conditions of use, in general practice. In a multicenter, open clinical trial, 669 patients (mean age: 47 years +/- 12; male: 245, female: 424) fulfilling the DSM IV criteria for pain disorder (of gastrointestinal localization), were included by 321 general practitioners (GP) and treated for 6 weeks with sulpiride 150 mg/d. Investigators' evaluations were planned at D14 and D42. Furthermore a diary was given to each patient for self evaluation and intercurrent events reporting. The pain was of psychological type in 93% of cases and caused social or working disabilities in 78% of patients. At inclusion the mean score of the Hamilton Anxiety Rating Scale was 18 +/- 8, and the mean score of the depression scale HARD (Humeur, Angoisse, Ralentissement, Danger) was 14.8 +/- 6.4. During the study 7.9% of the patients had at least one adverse event, and 3% of patients were withdrawn for adverse event. Safety assessed with a specific variable (grouping together adverse events' reporting and results of CGI item 3) was good for 88% of patients. The principal criterion of efficacy was the clinician's evaluation of the intensity and frequency of abdominal pain on a four-point scale from 0 (asymptomatic) to 3 (important/continuous) from D0 to D End a decrease in pain intensity (91% of patients) and in pain frequency (89%) was observed as well as in frequency and intensity of related gastroenterological symptoms such as disturbances of bowel movements (79% and 78%), bloated symptoms (88% and 83%), nausea/vomiting (90% and 90%). A similar improvement (p < 0.001) was observed from D0 to End point on the self evaluation parameters (Visual Analogic Scales), assessing pain (mean score D0-D End: 17.1 +/- 15.9), quality of sleep (mean score D0-D End: 27.1 +/- 17.8), activity (mean score D0-D End: 24.4 +/- 18.8), and appetite (mean score D0-D End: 22.6 +/- 16.6). In conclusion these results confirm the usefulness of sulpiride in the treatment of pain disorders a symptomatology known to cause difficulties to GP's in their practice.