1. Bolus i.v. doses of 14C-propofol (7-10 mg/kg) to rat, dog and rabbit, or an infusion dose (0.47 mg/kg per min for 6 h) to dog were eliminated primarily in urine (60-95% dose); faecal elimination (13-31%) occurred for rat and dog, but was minimal (less than 2%) for rabbit. 2. After bolus administration, blood 14C concentrations were maximal (8-30 micrograms equiv./ml) at 2-15 min; these declined rapidly during the 0-2 h period and thereafter more slowly. Propofol concentrations were maximal (4-16 micrograms/ml) at 2 min and the profiles were best fitted by a tri-exponential (rat and dog) or bi-exponential (rabbit) equation. Duration of sleep ranged from 5 to 8 min. 3. Infusion of 14C-propofol in dog gave a blood 14C concentration of 117 micrograms equiv./ml at the end of the 6 h infusion period; this declined at a similar rate to that after the bolus dose. Propofol concentration on termination of infusion was 13 micrograms/ml; thereafter, propofol concentrations declined less rapidly than after the bolus dose. Waking occurred about 44 min post-infusion. 4. Propofol was cleared by conjugation of the parent molecule or its quinol metabolite; hydroxylation of an isopropyl group also occurred in rat and rabbit. Biliary excretion leading to enterohepatic recirculation, and in turn increased sulphate conjugation, occurred in rat and dog, but not rabbit, resulting in a marked interspecies variation in drug clearance and metabolite profiles.