The present study determined the effect of halothane on arterial and venous propranolol concentrations during a continuous intravenous infusion of propranolol. Arterial and venous concentrations of propranolol remained constant during the experiment in the group of dogs anesthetized only with pentobarbital. However, there was a rapid increase in arterial propranolol concentration from 88 +/- 10 ng/ml (mean +/- SEM) prior to halothane to 116 +/- 12 ng/ml (P less than 0.05) and 130 +/- 7 ng/ml (P less than 0.05) 60 and 120 min, respectively, after starting halothane anesthesia (2.0 MAC 1.74%). The increase in venous propranolol concentration lagged substantially behind that of the arterial concentration, so that, 60 min after starting halothane, the arterial to venous (A/V) concentration ratio increased from 1.13 +/- 0.05 to a maximum of 1.48 +/- 0.08. In contrast to the changes following halothane, no significant change in the A/V ratio occurred following fentanyl. Both halothane and fentanyl administration produced a small but significant increase in the free fraction of propranolol (P less than 0.05). The results from this study emphasize the importance of the choice of sampling sites in pharmacokinetic experiments, as well as excluding subtle pharmacokinetic changes during anesthesia before ascribing changes in drug effect to changes in sensitivity to the drug.