OBJECTIVE: To test the existence of gene-by-stress interaction by assessing cardiovascular stress reactivity in monozygotic and dizygotic twins. METHODS: We studied 160 adolescent (mean age 16.7 ± 2.0 years; range 13-22 years) and 212 middle-aged twin pairs (mean age 44.2 ± 6.7 years; range 34-63 years). Systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR), pre-ejection period (PEP), and respiratory sinus arrhythmia (RSA) were measured at rest and during a choice reaction time and a mental arithmetic task. We used a bivariate analysis of the resting and mean stress levels to test for gene-by-stress interaction, which can be caused by the emergence of new genetic variance specific to stress or by stress-induced amplification of the existing genetic variance at rest. RESULTS: Genetic factors significantly contributed to individual differences in resting SBP, DBP, HR, PEP, and RSA levels in the adolescent (heritability range 0.31-0.70) and middle-aged (heritability range 0.32-0.64) cohorts. The effect of these genetic factors was amplified by stress for all variables in the adolescent cohort, and for SBP in the middle-aged cohort. In addition, stress-specific genetic variation emerged for HR in both cohorts and for PEP and SBP in the adolescent cohort. Heritability of stress levels of SBP, DBP, HR, PEP, and RSA ranged from 0.54 to 0.74 in the adolescents and from 0.44 to 0.64 in the middle-aged cohort. CONCLUSIONS: Stress uncovers genetic variance in BP, HR, and cardiac sympathovagal balance through the emergence of new stress-specific genetic effects and the amplification of existing genetic effects that also affect the resting values. Copyright © 2007 by American Psychosomatic Society.