We have investigated the effect of loperamide (4 mg tds) on the continence to a standard volume of rectally infused saline and anorectal manometry in 26 patients complaining of chronic diarrhea complicated by fecal incontinence and severe urgency. Each patient was treated for one week with loperamide (4 mg tds) and for one week with an identical placebo in a double-blind cross-over trial. Our results showed that as well as its established effects of improving stool consistency and reducing stool weight, frequency and episodes of incontinence and severe urgency, loperamide also significantly improved continence to a standard volume of rectally infused saline. This action was associated with an increase in the maximum basal sphincter pressure, an increase in the rectal volume required to abolish recovery of the rectoanal inhibitory reflex, and a reduction in rectal compliance. These results suggest that loperamide may have a specific action on the anal sphincter, which may aid continence in patients who complain of diarrhea and fecal incontinence.