AbstractBetaxolol is a selective antagonist of β1‐adrenergic receptors. Personal response to the drug widely varies and depends on its properties and individual features including innate characteristics. Our aim was to study the association between the clinical response to betaxolol in patients with essential hypertension (EH) and polymorphous markers of two genes: β1adrenergic receptor gene (ADRB1) and cytochrome P450 2D6 gene (CYP2D6). Eighty‐one patients with EH were selected. Mean age was 52.2 ± 1.22 years. Betaxolol monotherapy provided effective blood pressure control (BP < 140/90 mmHg) in 68 patients, 56 of them continued treatment with initial dose. The systolic (SBP) and diastolic (DBP) blood pressure declined significantly at the end of the study. We have not found any significant association of rest and exercise BP and heart rate (HR) with polymorphous markerArg389GlyofADRB1gene except the nighttime variability of DBP. But in case of the polymorphous markerPro34SerofCYP2D6gene we have found significant association with response to betaxolol therapy. The rest HR declined more significantly inSer/Progenotype carriers (−32.6 ± 4.77 beats/min and −18.4 ± 2.01 beats/min,P = 0.023). These patients demonstrated more significant increase of exercise time (4.58 ± 0.90 and 0.59 ± 0.58 min,P = 0.045). Maximal exercise HR and DBP were also significantly lower inSer/Progenotype carriers in comparison withSer/Sergenotype carriers. Decline of mean daytime SBP in 24‐h ambulatory blood pressure monitoring was more significant inProallele carriers (−21.0 ± 2.55 mmHg vs. −5.2 ± 2.27 mmHg in patients withSer/Sergenotype,P = 0.001). Betaxolol effect on HR and BP significantly depends on variability of the gene determining the drug metabolism. The carriers ofPro34allele ofCYP2D6gene (8.6%) are more sensitive to betaxolol therapy. Because of the relatively small group sizes our data should be considered as preliminary ones. The increase of our groups and the replication in other studies will permit to estimate the contribution of genetic factors to betaxolol effect on HR and BP.