Median lethal dose (LD50) of undiluted liquid insect repellent N,N-diethylphenylacetamide (DEPA) in male mice, rats and rabbits was 900, 825 and 635 mg/kg respectively when administered by gavage. Signs of DEPA intoxication point to stimulation of central nervous system (CNS). Acetazolamide (10 mg/kg), sodium bicarbonate (40 mg/kg), and atropine (5 mg/kg) when injected (ip) 5 min after a lethal oral dose of DEPA (1700 mg/kg) did not prevent mortality, while sodium pentobarbital (SPB; 20 mg/kg) when injected 5 min after or 15 min before DEPA provided greater protection to the animals. SPB pretreatment elevated the LD50 of DEPA to 1780 and 1535 mg/kg in mice and rats respectively and 85% rats survived when SPB was injected 5 min after acute oral exposure to DEPA (1000 mg/kg). Carboxylesterase (CaE) inhibition is not a factor in the protection mechanism of SPB. DEPA (1000 mg/kg) when given orally elevated blood PCO2 and reduced pH, O2 content and per cent O2 saturation, while administration of SPB after the same dose of DEPA reduced the degree of acidosis and raised PCO2, and increased the O2 content and per cent O2 saturation to near normal status. The CNS depressant action of SPB may be a crucial factor in protection of rats from DEPA poisoning.