People exposed to high partial pressures of oxygen, such as scuba divers, risk the onset of central nervous system oxygen toxicity (CNSOT). CNSOT presumably results from an accumulation of free radicals such as reactive oxygen species in the brain and produces epilepsy-like grand mal seizures, which may be fatal in an underwater environment. Many divers also use the neuro-excitatory drug pseudoephedrine (PSE) to reduce sinus inflammation. Incident reports from the Divers Alert Network (DAN) suggest a link between PSE use and an increased risk of diving accident or injury. The purpose of this study was to determine whether or not increasing doses of PSE decrease the latency to seizure (LS). Male and female rats (250 to 350g) were included so that gender-dependent differences could also be elucidated. Rats were surgically implanted under isoflurane anesthesia with radio-telemetry units, which allowed measurement of electroencephalograms without restraint. One week after surgery, each rat received a single 1 mL dose of PSE in saline (0, 40, 80, 100, 120, 160, and 320 mg/kg) via oral gavage. Nine rats were included in each group. Rats breathed 100% oxygen during a dive to 5 atmospheres absolute in a hyperbaric chamber. LS was defined as the duration of time between reaching maximal pressure and onset of seizure (increased electroencephalogram activity coupled with tonic-clonic spasms of forelimbs and head). Data are presented in Table 1 (mean ± SEM). Males exhibited decreased LS and decreased variability with increased dosage. The decrease in LS was significant at 100 mg/kg and higher. Females exhibited decreased LS following doses of 80 mg/kg, 100 mg/kg, and 320 mg. The decreases at 120 mg/kg and 160 mg/kg did not reach statistical significance, apparently due to increased variability. There were no significant differences between males and females. We conclude that only high doses of PSE decrease LS. Further testing is underway to determine the effects of menstrual cycle phase, age, and history of pregnancy on LS in female rats. The first two authors contributed equally.