The primary route of elimination of granisetron is by oxidative hepatic metabolism, thus its pharmacokinetic profile may be altered by co-administration of other drugs that inhibit or induce hepatic drug metabolizing enzymes. This open-label study investigated the effect of inhibition of cimetidine, a potent inhibitor of CYP1A2, CYP2D6 and CYP3A4, on the pharmacokinetic profile of intravenous granisetron in healthy male volunteers. Subjects (n = 12; 18-60 years) received granisetron (40 microg kg(-1)) infused over 3 min, six days before and on the eighth day of dosing with cimetidine (200 mg, four times a day). Blood samples were taken for pharmacokinetic analysis at intervals over 48 h following the administration of each dose of granisetron. Clinical chemistry, haematology and urinalysis were performed before, and 24 h after, each infusion. Electrocardiogram (ECG), resting blood pressure (BP) and pulse were monitored. There were no significant changes in the ECG, lead II trace or ECG time intervals, pulse or blood pressure on each study day. Minor falls in pulse rate and BP (likely to be related to recumbent posture) were seen during both granisetron dosing days, lasting 2 h after each infusion. No significant changes were apparent in the clinical chemistry, haematology or urinalysis measurements following granisetron dosing. No pharmacokinetic parameters measured after cimetidine administration were significantly different from those taken before. Adverse events were mild-to-moderate in severity and were similar to those reported in other studies with granisetron. The pharmacokinetics of granisetron, when administered as a single dose, appeared to be unaltered by cimetidine, an inhibitor of multiple hepatic enzymes (CYP1A2, CYP2D6 and CYP3A4). Granisetron was equally well tolerated before and after repeated dosing with cimetidine.