Plasma morphine levels and the area under the plasma concentration-time curve (AUC) after i.v. (10 mg kg-1), p.o. (100 mg kg-1) and rectal (unrestricted or restricted to 1.5 cm from the anus, 10 mg kg-1) administration of morphine hydrochloride were determined in 10 or 11-week-old male Wistar rats to compare bioavailability of morphine after the rectal dosage with that after oral administration. The AUC value after oral administration (15 micrograms min mL-1), which was normalized by the dose, was only one-tenth of that after i.v. dosing (151 micrograms min mL-1). In contrast, the AUC after rectal administration (unrestricted, 133 micrograms min mL-1; restricted, 142 micrograms min mL-1) was almost comparable with that after i.v. administration. From the comparison of these AUC values, the extent of systemic availability of morphine after rectal (unrestricted or restricted) and p.o. administration was estimated to be approximately 90 and 10%, respectively.