This investigation examines whether serum lipoprotein levels in patients with diabetes mellitus and in those with coronary artery disease are associated with lower heart rate variability (HRV). The study group consisted of 58 subjects divided into 3 groups: normal subjects, chronic stable angina, and type 1 diabetes. Twenty-four-hour ambulatory electrocardiographic recordings were analyzed in the time and frequency domains; standard instantaneous autonomic testing was also performed. On 24-hour ambulatory recordings, patients with chronic stable angina had significantly lower HRV than normals, and diabetics had a more marked reduction in HRV than both normals and anginal patients. When anginal patients and diabetics were stratified by total serum and low-density lipoprotein (LDL) cholesterol levels, diabetics with elevated total and LDL cholesterol had an additional, significant decrease in HRV parameters. No such difference was demonstrated in patients with stable angina. No significant correlations were noted for high-density lipoprotein (HDL) cholesterol, triglycerides, or total cholesterol/HDL ratio and HRV in diabetics or patient with angina. Diabetics with markedly abnormal peripheral reflexes had significantly higher triglycerides and total cholesterol/HDL ratios. Finally, standard tests of autonomic function did not correlate with total, LDL, HDL cholesterol levels, total cholesterol/HDL ratio, or triglycerides. Thus, we found a relation between atherogenic lipid levels and reduced HRV in diabetic patients that has not been previously identified.