The effect of metronidazole was studied in 21 consecutive patients with chronic unremitting perineal Crohn's disease. Drainage, erythema, and induration diminished dramatically in all patients, and complete healing was obtained in 10 of 18 patients maintained on therapy. Five others have shown advanced healing; in 2 patients the inflammation is improved, but healing is minimal. Side effects of metallic taste, dark urine, and mild gastrointestinal upset occurred in many patients. However, the dosage had to be decreased in only 4 patients and the drug discontinued in 1 patient, all because of peripheral neuropathy that proved to be reversible. In 2 other patients, metronidazole was discontinued because of poor compliance. If further experience corroborates this prompt and striking response in patients with extreme, disabling, and otherwise unmanageable disease, metronidazole will play an important role in the therapy of perineal Crohn's disease.