The effects of erythromycin, clarithromycin and rokitamycin on the metabolism of nifedipine were studied in vitro and in situ. Erythromycin, clarithromycin or rokitamycin added to nifedipine did not inhibit the formation of metabolite, M-1, of nifedipine, whereas pretreatment with erythromycin or clarithromycin significantly (p < 0.05) inhibited its formation. Only erythromycin significantly (p < 0.05) inhibited the formation of M-2 from M-1. These observations agreed with the results obtained using an in situ rat intestinal loop technique. As assessed by the concentrations of nifedipine and M-2 in jugular and portal vein blood, the inhibition of nifedipine metabolism by erythromycin was greater after multiple doses than after a single dose. Moreover, our results suggest that rokitamycin is a less potent inhibitor of nifedipine metabolism.