The site of hydrolysis of etomidate, a new intravenous anesthetic, and effects of bis-(P-nitrophenyl) phosphate (BNPP), a specific inhibitor of the hepatic microsomal hydrolase, on the duration of action and elimination of etomidate were investigated. Etomidate concentrations ranging from 0.1 to 1.0 μg/ml were incubated with fresh human and canine plasmas. Half the samples were treated with potassium fluoride solution to inhibit the esterases. Sleep times and the plasma kinetics of etomidate were investigated in two groups of dogs, half of which received etomidate, 1.6 mg/kg alone; the other half were pretreated with BNPP. There was no significant change in the concentration of etomidate after incubation with plasma in the presence or absence of fluoride. Dogs that received etomidate alone (controls)slept 4.8±1.0(SEM) min after the first injection and 4.6±0.9 min after the second. The difference was not statistically significant. In the study group, mean durations of sleep were 4.6±1.2 min after the first injection and 7.2±0.9 min after BNPP treatment. The difference was significant (P<0.01). Plasma clearances of etomidate were 37±4 l/hour in the control group and 31.9±2.8 l/hour in the pretreated group. The difference was not significant. It is concluded that etomidate is not hydrolyzed in human or canine plasma. The hypnotic action of the drug is prolonged after treatment with BNPP, but the mechanism of this interaction remains to be elucidated.