Hyperbaric oxygen has been used in the management of perianal Crohn's disease on the assumption that tissue oxygenation is impaired. The Dead Sea region of Israel is the lowest point on earth (402 m below sea level), and therefore the oxygen pressure is increased. We hypothesized that this elevation in oxygen pressure over an extended time might be as effective as shorter periods of high-pressure oxygen in a hyperbaric chamber. So we investigated whether the Dead Sea environment might affect the activity and perianal complications of Crohn's disease. Six patients with Crohn's disease unresponsive to medical treatment spent periods of 1–3 weeks at the Dead Sea. Four patients had discharging perianal fistulas. All were given advice concerning diet, physical activity, and immersion in the Dead Sea. The Clamp–Softley modification of the Harvey–Bradshaw Crohn's disease activity index was used to assess disease activity initially and at weekly intervals during treatment. Drug therapy was tailored to patient symptoms. Mean disease activity index before treatment was 9.0 ± 1.4 (mean ± SEM) and after a week at the Dead Sea 3.5 ± 0.3 (p = 0.006). After 2 weeks the index decreased to 2.0 ± 0.4 (p = 0.037) in four patients. In one patient complete healing of perianal fistulae occurred after 2 weeks, and in two others there was striking improvement. Two patients with active Crohn's disease and on high-dose corticosteroids were able to stop all medication during their stay. Decrease in activity index occurred rapidly, whereas the improvement in perianal disease was more gradual. The Dead Sea environment was highly effective in managing patients with severe Crohn's disease, including perianal complications in this small, uncontrolled series.