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Normobaric supplemental oxygen can prolong seizures not caused by hyperbaric oxygen therapy. In addition, hyperbaric oxygen therapy can cause seizures. The mechanism of hyperbaric oxygen-induced seizures is unknown. We hypothesized that pretreatment with pyridoxine may delay the onset of hyperbaric oxygen-induced seizures, recognizing that pyridoxine is already an antidote for some epileptogenic poisons such as isoniazid and monomethylhydrazine. Therefore, rats were pretreated with intraperitoneal injections of pyridoxine at 48, 24, and 2 h before undergoing hyperbaric oxygen (HBO) treatment at 3 atmospheres absolute with 100% oxygen and were compared to a control group of HBO-treated rats for time to onset of seizures. There was no difference in onset of seizure time between the pyridoxine-treated group of rats and the control rats. Supplemental pyridoxine pretreatment did not alter the time to onset of seizures during HBO treatment in this study.