['Controlled decompression from saturation conditions is not always an option, particularly in a disabled submarine scenario. Hypothesis Prophylactic high dose methylprednisolone (MP) would improve outcome in severe cases of decompression sickness (DCS).', 'Littermate pairs of male Yorkshire swine (n = 86, mean weight +/- SE = 19.3 +/- 0.2 kg) were randomized to one of three groups, then compressed on air to 4.3 ATA (33 msw) for 22 h and brought directly to surface pressure (1 ATA) at 0.9 ATA x min(-1). The MP-50 group received i.v. infusion of 50 mg x kg(-1) of MP dissolved in 60 cc normal saline (NS) immediately prior to the hyperbaric exposure. The NS group received 60 cc NS i.v. immediately prior to the hyperbaric exposure. The MP-10 group received i.v. infusion of 10 mg x kg(-1) MP dissolved in 60 cc NS during the hyperbaric exposure, 7 h before the decompression.', 'Outcomes of severe DCS and death were recorded. NS group: 14 DCS, 4 died; MP-50 group: 19 DCS, 12 died; MP-10 group: 19 DCS, 10 died. Compared with the NS group, logistic regression analysis suggested that animals in the MP-10 group were more likely to get severe DCS and to die (p < 0.01) and animals in the MP-50 group were more likely to die from their disease (p < 0.01).'] Does prophylactic high dose methylprednisolone fail to treat severe decompression sickness in swine?