This study was conducted to determine the effect of clarithromycin (CAM) on the bioavailability of cyclosporin (CYA) in rats, and to compare its effect with that of erythromycin (EM). The area under the blood CYA concentration-time curve (AUCi.v.) values after intravenous administration of CYA (2 mg/kg) in combination with CAM or EM (100 mg/kg, p.o.) were significantly increased compared with those of CYA alone, suggesting that there was metabolic inhibition of CYA in the liver by CAM or EM. The time to reach the peak concentration after oral administration of CYA (10 mg/kg) tended to be longer with increasing doses of both CAM and EM (10 and 100 mg/kg, p.o.). Each AUCp.o. value for the CAM or EM coadministration group, except the EM (100 mg/kg) coadministration group (about 77% increase), was comparable to that for the CYA alone group. Both CAM and EM (10 and 100 mg/kg, p.o.) were shown to delay gastric emptying in a dose-dependent manner. The gastric emptying in the group treated with CAM (100 mg/kg) was significantly lower than that with EM (100 mg/kg). It is suggested that CAM as well as EM might affect the oral bioavailability of CYA by inhibiting its metabolism and simultaneously by changing the gastrointestinal motility in rats. Thus, caution is recommended when administering CYA concomitantly with CAM to humans.