Several uncontrolled studies have suggested a beneficial effect of hyperbaric oxygen on multiple sclerosis. We studied 40 patients with advanced chronic multiple sclerosis who were randomly divided into two matching groups. The experimental group received pure oxygen, and the placebo group received a mixture of 10 per cent oxygen and 90 per cent nitrogen; both groups were treated at a pressure of 2 atmospheres absolute for 90 minutes once daily, for a total of 20 exposures. Objective improvement occurred in 12 of 17 patients treated with hyperbaric oxygen and in 1 of 20 patients treated with placebo (P less than 0.0001). Improvement was transient in seven of the patients treated with oxygen and long-lasting in five. Those with less severe forms of the disease had a more favorable and lasting response. At one year of follow-up, deterioration was noticed in 2 patients (12 per cent) in the oxygen group, neither of whom had had an initial response, and in 11 patients (55 per cent) in the placebo group, one of whom had had a positive initial response (P less than 0.0008).