Fistulas complicating Crohn's disease often are refractory to medical management. Immunosuppressive therapy is sometimes effective but requires several months before efficacy can be determined. We treated five patients with Crohn's disease complicated by chronic draining fistulas unresponsive to previous surgery, steroids, antibiotics, total parenteral nutrition, 6-mercaptopurine, or azathioprine with continuous infusion cyclosporin A (CyA). The five patients had a total of 12 fistulas (five enterovaginal, three perianal, three enterocutaneous, one enterovesical). CyA was administered initially at 4 mg/kg/day for 6-10 days, after which oral dosing was begun at 8 mg/kg/day and adjusted to maintain trough serum levels of 100-200 ng/ml. All fistulas responded to CyA infusion with decreased drainage and with improvement in both perifistular inflammation and patient comfort. Complete resolution of drainage was seen in 10 of the 12 fistulas. Initial response was seen after a mean of 3.6 days (range, 2-5 days) with complete cessation of drainage in the 10 fistulas after a mean of 7.9 days (range, 3-28 days). Therapy was continued for a mean of 6.2 months (range, 1.5-18 months). Relapse was seen in two perianal fistulas (3 wk and 7 months) and in two enterovaginal fistulas (1 and 2 months). Two of these recurrences corresponded to lowered serum levels of CyA. An enterocutaneous fistula also recurred after 2.5 months, associated with a distal stricture that required resection. Side effects were minor except for a mycotic aneurysm in one patient which occurred after 7 months of treatment. Intravenous CyA may prove to be a useful agent in the initial management of refractory Crohn's disease fistulas, although relapse as serum levels are lowered and infectious complications are limiting factors for long-term use as a single agent.