While the β2-adrenoceptor pathway is essential for cardiovascular regulation, the impact of ADRB2 gene variations on circulatory responses is unclear, possibly due to neural compensatory mechanisms. We tested the hypotheses that (i) sympathetic block by thoracic epidural anaesthesia (TEA) unmasks the influence on arterial pressure of genetic variations and (ii) vasopressor requirements during TEA depend on ADRB2 gene variation.Ninety-three elective patients undergoing abdominal surgery were included prospectively. After epidural bupivacaine 0.5% (15 mg test dose+50 mg), arterial pressure, heart rate, and progression of sensory block were measured for 20 min in the supine awake state and for 20 min after standardized anaesthetic induction of general anaesthesia. The primary endpoint was cumulative dose of the α-adrenoreceptor agonist phenylephrine administered to sustain a mean arterial pressure >70 mm Hg. The ADRB2 polymorphisms Arg16Gly and Gln27Glu were genotyped using Slowdown-PCR.After TEA, 86 (93%) patients required phenylephrine. The mean dosages (sd) were significantly different between the ADRB2 genotypes [Arg16Arg 357 µg (326), Arg16Gly 776 µg (449), Gly16Gly 600 µg (443), P=0.036; Gln27Gln 356 µg (254), Gln27Glu 639 µg (354), Glu27Glu 577 µg (388), P=0.007]. Multiple linear regression analysis revealed that age, male gender, rostral extent of sensory block, lower arterial pressure before TEA, and ADRB2 Glu27 allele together explained 37% of phenylephrine dosage variation, with genetic variants being the second most important predictor (10%; P<0.001).The ADRB2 Glu27 allele is an independent predictor of arterial hypotension and vasopressor requirements after TEA. Neural block can unmask genetic influences on neurohumoral regulation. Clinical trial registration DRKS00005260.