In order to develop a suitable beagle dog model for evaluating the bioavailability of a sustained-release dosage form, we tried to control the gastrointestinal (GI) transit time in beagle dogs so as to make it similar to that in humans by means of pharmacological modification of GI motility using loperamide hydrochloride, an antidiarrheal drug. Acetaminophen showed greater absorbability from jejunum and ileum than that from colon in rats. Relative bioavailability of acetaminophen from a sustained-release dosage form after oral administration (31%) in beagle dogs, compared with a solution as reference dosage form, was obviously lower than that (90%) in humans, probably because of the shorter GI transit time. The bioavailability was significantly increased (2-fold) in beagle dogs treated with loperamide hydrochloride (0.12 mg/kg). Treatment with loperamide did not exert any significant effects on the clearance of acetaminophen, but did increase the GI transit time from 3.5 to 5.0 h. In this study, it was suggested that GI transit controlled-beagle dog would be effective enough to avoid the underestimation of the bioavailability of a sustained-release dosage form containing a drug with site-specific GI absorption, such as acetaminophen.