We tested the hypothesis that blood pressure (BP) responses to physical and mental stress are associated with polymorphisms in the β-2 adrenergic receptor (AR) gene. We studied normotensive, young, monozygotic (MZ) and dizygotic (DZ) twins. The subjects underwent automated BP measurements at the brachial and digital arteries and were subjected to mental arithmetic and cold pressor stress. We used allele-specific PCR to genotype four single nucleotide polymorphisms in the β-2 AR gene. The most functionally relevant polymorphism in the β-2 AR gene, Arg16/Gly, was associated with systolic and diastolic BP under resting conditions, during mental arithmetic, and during the cold pressor test, as well as with the increase in diastolic BP during both forms of stress. These findings support a role for the β-2 AR gene in BP regulation. They also indicate that the β-2 AR gene influences the level of not only resting but also stress-related BP.