Purpose: Lotronex is a potent and selective 5-HT3 receptor antagonist indicated in women for the treatment of diarrhea predominant IBS. Constipation is a common side effect of treatment with drugs in this class. In earlier trials, constipation was reported in 28% and 5% of Lotronex and placebo treated subjects, respectively. In these trials, laxative use was not allowed and 10% of Lotronex treated subjects discontinued therapy due to constipation. This study evaluated the use of laxatives for the constipation management in Lotronex treated subjects. Method: This trial was a 12-week randomized, double-blind, placebocontrolled, multi-center study of Lotronex 1 mg twice daily for the control of bowel urgency in 801 females with nonconstipated IBS. Improvement in IBS symptoms were reported using the seven-point IBS Global Improvement Scale (GIS) ranging from substantially improved to substantially worse. Responders were defined as those reporting substantial or moderate improvement at the final visit. All subjects were dispensed Milk of Magnesia and instructed to use the medication if needed as directed by the investigator. Results: Constipation was reported by 39% and 14% of subjects in the Lotronex and placebo groups, respectively. Of the Lotronex group reporting constipation, 61% had a single episode, and 81% used laxative to manage their constipation. Five percent of Lotronex treated subjects reported constipation, used laxative, and withdrew from the trial secondary to constipation. A significantly greater number of Lotronex treated subjects were GIS responders at the final visit compared to placebo (78% and 45%). This positive response was seen in the Lotronex group reporting constipation (84%) as well as those who did not (74%). Further, there was a similar proportion of GIS responders in the Lotronex group using laxative therapy (76%) as those who did not (74%). Constipation was the only adverse event occurring significantly more frequently with Lotronex than placebo. Conclusion: Use of laxative to manage constipation in Lotronex treated subjects reduced the proportion of subjects who withdrew from therapy compared to earlier trials without negatively impacting the therapy’s benefit. This study was sponsored by Glaxo Wellcome, Inc.