The disposition of propranolol was studied, using dual-route administration, in two groups of six dogs. Each dog was studied on three consecutive days: day 1 awake, day 2 during anaesthesia, and day 3, 24 h after anaesthesia. Anaesthesia was with isoflurane 2.0 MAC (in oxygen) in one group and with a fentanyl-nitrous oxide-atracurium regimen in the other group. In the group receiving fentanyl, anaesthesia caused a significant decrease (63%) in intrinsic clearance from the day 1 value (P less than 0.05) and a 45% decrease in systemic clearance (P less than 0.05). Hepatic plasma flow decreased by 27% (ns). A similar pattern was found with isoflurane: intrinsic clearance decreased by 53% (P less than 0.05) and systemic clearance by 40% (P less than 0.05). Hepatic plasma flow decreased by 40% (ns). In both groups, the values 24 h after anaesthesia were not significantly different from those obtained on day 1. Anaesthesia with either fentanyl-nitrous oxide-atracurium or isoflurane has a marked, but short-lasting effect on the disposition of propranolol, in part as a result of a decrease in intrinsic clearance.