BACKGROUND: Neuroticism is widely used as an explanatory concept in etiological research of psychopathology. In order to clarify what neuroticism actually represents, we investigated the genetic association between neuroticism and cardiovascular measures. METHOD: In 125 female twin pairs (18-30 years), electrocardiogram and continuous finger blood pressure were assessed during two rest and two mental stress conditions. Mean values for baroreflex sensitivity (BRS), heart rate variability (HRV) and inter-beat interval (IBI) were calculated for each condition. Neuroticism was assessed by multiple questionnaires. Multivariate genetic model-fitting analyses were used to investigate the genetic correlation between latent neuroticism and the cardiovascular autonomic nervous system (ANS) measures. RESULTS: Neuroticism was negatively correlated to BRS and HRV. Neuroticism was not correlated to IBI. For BRS, this phenotypical relation was entirely determined by shared genetic influences. For HRV, the genetic contribution to the phenotypical correlation was not significant, but the proportions of explained covariance showed a trend of more genetic than environmental influences on the phenotypical relationship. CONCLUSIONS: High neuroticism is associated with a deregulated ANS. Pleiotropic genetic effects may be partly responsible for this effect.