In 6 healthy volunteers the pharmacokinetics of bisoprolol under steady-state conditions was investigated over three consecutive phases: over 7 days of 10 mg of bisoprolol once daily per os, 7 days of 10 mg of bisoprolol once daily plus 400 mg of cimetidine t.i.d. and 14 days of 10 mg of bisoprolol and 600 mg of rifampicin once daily with adequate intervals free of medication. After therapy with bisoprolol alone peak plasma levels (Cssmax) of the beta-blocker were 55.5 +/- 6.4 ng/ml (means +/- SEM), area under the plasma level-time curve (AUC tau) was 597 +/- 70 ng/ml.h, total body clearance (CL) 15.8 +/- 1.8 l/h and elimination half-lives (t1/2 beta) 10.1 +/- 1.2 h. Cimetidine did not cause any significant changes in the pharmacokinetics of bisoprolol. Co-administration of rifampicin resulted in a decrease in Cssmax (43.0 +/- 6.9 ng/ml), AUC tau (397 +/- 54 ng/ml X h) and t1/2 beta (6.2 +/- 0.4 h). Accordingly, total body clearance increased to 23.8 +/- 2.5 l/h (p less than 0.05). In conclusion bisoprolol showed a statistically significant but probably clinically not important interaction with the enzyme-inducing drug rifampicin, but not with the enzyme inhibitor cimetidine.