This is placebo-controlled study of three rifaximin doses in patients with DIBS. Subjects will be randomized to receive daily doses of placebo BID, rifaximin 275 mg BID, rifaximin 550 mg BID, or 1100 mg BID for 14 days. These four groups will subsequently receive an additional two weeks of placebo for a total of 4 weeks of treatment. A fifth group of subjects will receive rifaximin 550 mg BID for a period of 28 days. Subjects who successfully respond to treatment at the end of the 28-day Treatment Phase will be followed in a Post-treatment Phase that includes study visits during Weeks 6, 8, 12 and 16. Subjects who relapse during the Post-treatment Phase will be discontinued from the study.

While IBS is one of the most common chronic medical conditions the etiology of IBS is unknown. Although not a life-threatening illness, IBS is considered to be a serious condition that has a substantial impact on a subject's day-to-day function. IBS is characterized by abdominal pain and altered bowel habits, including diarrhea, constipation, or alternating diarrhea and constipation. Symptoms are typically intermittent but may be continuous.

Inclusion Criteria:

1. Male or female subject 18 years of age or older.
2. Irritable bowel syndrome confirmed by the Rome II Criteria
3. Lower endoscopic examination that demonstrates normal colonic anatomy

Exclusion Criteria:

1. Subject has exclusively constipation-predominant IBS (CIBS) that is characterized by < 3 bowel movements/week or hard and lumpy stools.
2. Subject has alternating IBS, but is currently presenting with constipation associated IBS symptoms.
3. Subject has had adequate control of their DIBS and their symptom of bloating the week preceding the screening visit or at the time of randomization. Bloating includes the following symptoms: abdominal fullness, bloating, gas, or swelling.
4. Subjects has a positive stool culture for O & P (ovum and parasite) and/or Clostridium difficile
5. Subject has failed to record 2 negative weekly global assessments during the past 10 days prior to randomization.