Depression and reduced heart rate variability (HRV) are predictors of coronary artery disease (CAD), and highly correlated with each other. However, little is known to what extend this correlation can be explained by common genetic components. We examined 198 middle-aged male twins (121 monozygotic and 77 dizygotic) from the Vietnam Era Twin Registry. Current depressive symptoms were assessed using the Beck Depression Inventory-II and HRV was assessed on 24-hour electrocardiographic Holter recordings. Five frequency domain variables were used, including ultra low frequency (ULF), very low frequency (VLF), low frequency (LF), high frequency (HF) and total power (TPow). Structural equation modeling was used to estimate shared genetic effects for depressive symptoms and the HRV frequency domains. Both depressive symptoms (h(2)=.5) and all measurements of HRV showed high heritability (h(2)=.43-.63). A significant inverse correlation was found between depressive symptoms and all HRV indices except LF and HF, with the highest coefficient (r) for TPow (r = -.24, P = .01) and ULF (r = -.24, P = .01). Bivariate genetic modeling revealed significant genetic correlations between depressive symptoms and TPow (r(A) = -.21, P = .04), as well as ULF (r(A) = -.23, P = .02). Of the total covariance between depressive symptoms and these two HRV indices, over 80% was due to the same genetic factors. In conclusion, depressive symptoms are associated with decreased HRV and this association is due, in large part, to a shared genetic effect. These results suggest that a common neurobiological dysfunction links depression and autonomic dysregulation.