Perianal involvement in Crohn's disease is common (< or = 50%), distressing, and frequently refractory to treatment. Clinical features include painful induration and stenosis, discharging fistulas, and fissures. The pathogenesis of these lesions is unclear, but local ischemia and secondary anaerobic infection may play a role. Following three sporadic reports of successful treatment with hyperbaric oxygen (HBO), we undertook a trial of this method in 10 patients with refractory perianal disease. These patients' perianal Crohn's disease had not responded to treatment that included local medications, salicylates, corticosteroids, metronidazole, or 6-mercaptopurine were treated. Treatment was administered in a hyperbaric chamber at a pressure of 2.5 atm absolute. Each session lasted 90 min, and each course consisted of 20 daily sessions. Complete healing occurred in 5 patients after one to two courses. In an additional 2, after three courses, 1 patient improved but did not heal, and 2 did not improve. No adverse effects were noted by any of the 10 patients. Follow-up of 18 months did not reveal any recurrence. These preliminary results confirm that HBO therapy is a safe and efficient therapeutic option for perianal Crohn's disease.