What is known and objective Nebivolol, a selective beta 1 adrenoreceptor antagonist, is predominantly metabolized by cytochrome P450 (CYP)2D6 and shows a wide interindividual variability in pharmacokinetics. The present study was conducted to evaluate the effects of the major CYP2D6 polymorphisms on nebivolol disposition in healthy Chinese volunteers. Methods Twenty-eight volunteers were enrolled and classified as CYP2D6*1/*1, CYP2D6*1/*10, CYP2D6*10/*10 and CYP2D6*5 carriers according to their genotypes. The concentration of nebivolol was determined by high-performance liquid chromatography-tandem mass spectrometry. The association between the pharmacokinetic parameters and genotypes was evaluated using the unpaired t test or analysis of variance. Results and discussion We evaluated the effects of CYP2D6*5 and *10 polymorphism on the pharmacokinetics of nebivolol. Plasma nebivolol peak concentration and area under the curve (AUC((0-48 h)) and AUC((0-infinity))) were significantly higher in subjects with CYP2D6*5 and CYP2D6*10/*10 polymorphism than those in subjects with wild-type CYP2D6 (CYP2D6*1/*1), whereas its plasma clearance was significantly lower in the CYP2D6*10/*10 and CYP2D6*5 carriers. No significant differences in the peak time and terminal half-life of nebivolol were observed among CYP2D6*10/*10, CYP2D6*1/*1 and CYP2D6*5 carriers. What is new and conclusion Both CYP2D6*5 and *10 polymorphism altered the pharmacokinetics of nebivolol in healthy Chinese volunteers. Further studies are required to investigate the effects of these single-nucleotide polymorphisms on the pharmacokinetics, pharmacodynamics and toxicity of nebivolol.