The disposition of (.+-.)- and (-)-propranolol and their glucuronic acid conjugates, (.+-.)-POG [propranolol-O-glucuronide] and (-)-POG, in plasma was determined in 5 dogs following single 160 mg oral doses of stable isotope labeled racemic propranolol. Each animal received 1 dose of the racemate with the (.+-.)-isomer labeled with 2 deuteriums and 1 dose with the (-)-isomer labeled. The isomers were separated and measured by gas chromatography-mass spectrometry. No stable isotope effect was detected. The area under the plasma concentration-time curve (AUC) for (-)-propranolol was only 54 .+-. 10% (mean .+-. SD; n = 10) of the AUC for (+)-propanolol. The AUC of (-)-POG exceeded the AUC of (+)-POG by 4.02 .+-. 1.22 times (mean .+-. SD; n = 10). The time to peak plasma concentration (3.9-4.3 h) and the half-life (1.6-1.9 h) were identical for both isomers of propranolol as well as of POG. These results demonstrate a significantly lower oral bioavailability of (-)- as compared to (+)-propranolol in the dog, which appears to be associated with stereoselective presystemic glucuronidation of (-)-propranolol.