Chronic liver disease, both alcoholic and nonalcoholic, has been shown to be associated with autonomic neuropathy, as well as other hemodynamic and circulatory disturbances. In a longitudinal study, the presence of autonomic neuropathy and the severity of liver disease were independent risk factors for mortality. The aim of this study was to determine whether the severity of liver disease correlated with measures of heart rate variability. We studied 21 patients being evaluated for liver transplantation to determine if severity of disease correlated with heart rate variability and compared them to seven healthy controls. Heart rate variability was determined for a series of 500 consecutive R-R intervals during quiet breathing. Standard deviation, pNN50, a marker of parasympathetic function, and approximate entropy (ApEn), a recently described measure of regularity, were calculated. Four standard tests of autonomic function were also performed. pNN50 was significantly reduced in all liver disease patients compared to controls (P < 0.05). Both standard deviation and ApEn were significantly reduced in Child's class C patients suggesting a generalized dysfunction in cardiovascular homeostasis. ApEn was significantly lower in the nonsurvivors during follow-up than the survivors (P < 0.05). In conclusion, increasing severity of liver failure is associated with a reduction in total heart rate variability and regularity. Measurement of heart rate variability offers a simple, noninvasive means of assessing the cardiovascular and autonomic effects of liver disease, particularly in those awaiting liver transplantation.