Functional constipation in children is a common problem in daily practice, however there is currently no accepted optimal treatment of choice. This study investigated the effect of cisapride in the treatment of pediatric constipation when combined with magnesium oxide (MgO). This prospective study enrolled children with chronic constipation. They were randomly assigned to either MgO (125 mg three times a day for patients weighing less than 20 kg or 250 mg three times a day for those weighing more than 20 kg), or cisapride 0.2 mg/kg (max 5mg/dose) plus MgO for 4 weeks. Twenty-one doctors in 19 major medical centers or hospitals in Taiwan with well- established pediatric departments participated in this study from October 1999 to March 2000. 84 children (51 males, 33 females, 1-7 years of age) with fewer than 2 spontaneous bowel movements per week for at least one month completed the study. After 1 week of therapy, a good response, defined as 3 or more bowel movements per week, was achieved in 30 (68.2%) of children treated with cisapride and MgO compared with 23 (57.5%) children treated with MgO alone (p=n.s.). At the end of the 4-week treatment period, 90.9% of the children in cisapride group compared with 67.5% of the children in MgO group achieved a good response (p=0.013). There was no statistical difference between the two groups in terms of the side effects and stool characteristics. In conclusion, it appears that cisapride in combination with MgO may have a synergistic effect and improves the frequency of stool passage in pediatric functional constipation.