Because of reports suggesting the efficacy of metronidazole therapy in the healing of perianal fistulae in Crohn's disease, the effect of metronidazole on symptoms of Crohn's disease and associated perianal fistulae were evaluated in eight consecutive patients. The criterion for entry into the study was the presence of resistant fistulae in patients with Crohn's disease. The duration of intestinal Crohn's ranged from 1/2-30 years and fistulae from 1-14 years. All patients had ileocolitis or pancolitis. Two had enteroenteric fistulae in addition to perianal fistulae. All had had previous surgery, half for fistulae and half for intestinal complications, usually obstruction. All had been on Prednisone. All but one had received multiple other drugs including Azathioprine, Azulfidine, antibiotics, and rectal steroids. Patients were placed on metronidazole 1000 to 1500 mg/day orally in divided doses. The number of draining fistulae was reduced 20-fold and the number of detectable fistulous openings by 50%. All patients had relief of fistula-associated pain; general Crohn's disease symptoms improved as well. Complete resolution of all symptoms occurred in half the patients. All patients experienced side effects, six had numbness of toes and five had metallic taste. Resolution of side effects occurred on discontinuation of metronidazole after 1-3 wk off the drug in all except one patient. All patients noted continued improvement in Crohn's symptoms during 6 months of follow-up after cessation of their therapy. Other side effects that have been reported with metronidazole therapy were not seen in our patients.