Background: Although it is known that a given level of strain does not induce a corresponding CHD risk in all individuals, factors that predict groups at risk have remained unclear. Neuregulin-1 (NRG-1) has various roles in the development and function of the heart and autonomic nervous system. Purpose: We examined whether polymorphic variation in NRG-1 moderates the association between job strain and early atherosclerosis. Methods: The participants (M age = 32.5) were 349 women and 357 men derived from the population-based Cardiovascular Risk in Young Finns study. Job strain was defined as the joint effect of job demands and job control. Preclinical atherosclerosis was measured using carotid intima-media thickness (IMT) ultrasound Results: NRG-1 single nucleotide polymorphism SNP8NRG221533 (T to C) was found to moderate the association between job strain and IMT in men (p =. 04). Job strain was significantly associated with increased IMT among men with TIT genotype but not among the others. A direct association between NRG-1 and IMT was found in women. Conclusions: Our results suggest that the effect of job strain on early atherosclerosis is dependent on NRG-1 genotype in men. Gene x Environment Interaction approach seems to offer important additional information in stress research.