Tegaserod relieves overall and multiple individual constipation-predominant irritable bowel syndrome (IBS-C) symptoms. However, mechanisms for the relief of abdominal pain/discomfort are not well understood. The effects of tegaserod on rectal sensitivity to distension were measured by the nociceptive flexion RIII reflex, as evidenced by spinal hyperexcitability (i.e. increase or facilitation of the RIII reflex), in IBS-C patients. A randomized, double-blind, placebo-controlled, parallel study was performed in 30 women with IBS-C. The effects of slow ramp rectal distension on the RIII reflex, recorded from the lower limb, were measured before [first experimental day (D1)] and after 7 days [day 8 (D8)] of placebo (n=15) or 6 mg tegaserod bid (n=15). Pressure-volume and sensation-volume relationships were measured during distension, and patients reported their IBS symptoms daily. On D1, rectal distension facilitated the RIII reflex in both treatment groups. On D8 vs D1 these facilitatory effects were significantly lower (P<0.001, analysis of variance) after tegaserod (mean reduction: -30.3+/-11.9%) than placebo (mean reduction: -10.1+/-12.9%). No significant changes in the volume-sensation relationship or differences in compliance were observed with tegaserod or placebo. In conclusion, tegaserod reduces the facilitatory effects of rectal distension on the RIII reflex in women with IBS-C.