Activation of the sympathoadrenal system (comprising the sympathetic nervous system and the adrenal medulla) in response to stressful stimuli is an important defence mechanism as well as a contributor to several cardiovascular diseases. There is variability in the sympathoadrenal system response to stress although the extent to which this is genetically regulated is unclear. Some rodent models, including the hereditary hyper-triglyceridemic (hHTg) rat, are hyper responsive to stress. We investigated whether quantitative trait loci (QTLs) that affect sympathoadrenal response to stress could be identified. Second filial generation rats (n = 189) derived from a cross of the hHTg rat and the Brown Norway rat had plasma noradrenaline (NAD) and adrenaline (AD) levels, indices of activation of the sympathoneural and adrenal medulla components respectively, measured in the resting state and in response to an immobilisation stress. Responses were assessed early (20 min) and late (120 min) after the application of the stress. A genome-scan was conducted using 153 microsatellite markers. Two QTLs (maximum peak lod scores of 4.17 and 3.52 respectively) influencing both the early and late plasma NAD response to stress were found on chromosome 10. Together, the QTLs accounted for approximately 20% of the total variation in both the early and late NAD responses in the F2 rats. Interestingly, the QTLs had no effect on plasma AD response to stress. These findings provide evidence for a genetic determination of the response of a specific component of the sympathoadrenal system response to stress. Genetically determined variation in sympathetic nervous system response to stress may contribute to cardiovascular diseases.