Etomidate, R-(+)-ethyl-1-(1-phenylethyl)-1H-imidazole-5-carboxylate was found to be a potent, short-acting and safe hypnotic; when given intravenously in single doses to mice, rats, guinea-pigs, rabbits and dogs. In rats of different body weight (50, 100, 200 and 300 g) two injection rates were used (2 sec and 2 min). By rapid iv injection in rats of 200 g etomidate (ED50 equal to 0.57 mg/kg) is about 6 times more potent than methohexital (ED50 equal to 3.51 mg/kg) and 25 times more potent than propanidid and thiopental (ED50's equal to 13.4 mg/kg). The safety margin (LD50/ED50) in these rats is 26.0 for etomidate, 9.5 for methohexital, 6.7 for propanidid and 4.6 for thiopental. Potency and toxicity of etomidate slightly increase with increasing injection rates without affecting the safety margin. The duration of hypnosis with etomidate is dose-dependent and the safety margin will therefore be widened when sleep of short duration is aimed at. Recovery after etomidate is very rapid. With lower body weights, higher doses in mg/kg are required for inducing hypnosis of comparable duration. No systematic differences were found after etomidate injection in incidence and duration of hypnosis nor in mortality between animals of different sex. ECG, blood pressure, haematological and biochemical analysis, urinalysis and histopathology did not reveal any drug-related adverse effect after daily injection of etomidate for 3 weeks in rats (highest dose 5.0 mg/kg) and 2 weeks in dogs (highest dose 1.50 mg/kg). No tolerance was observed after repeated administration. Etomidate is devoid of any teratogenic effect in rats (highest dose: 5.0 mg/kg daily from day 6 through day 15 of pregnancy), and in New Zealand white rabbits (highest dose: 4.5 mg/kg daily from day 6 through day 18 of pregnancy). The hypnotic effects of etomidate at very low dose levels in different laboratory animals are compared with the effects obtained in human subjects, in which successful induction of anaesthesia was obtained without producing any release of histamine and with only minimal effects on cardiovascular and respiratory functions.