To determine whether compositional abnormalities are present in high-density lipoprotein (HDL) in patients with insulin-dependent diabetes mellitus (IDDM) that might negate its putatively protective cardiovascular effects, we studied the plasma lipoproteins of 12 men with varying degrees of clinical control (mean fasting glucose 193 +/- 10 mg/dl, mean glycoalbumin greater than 73% above control mean). The diabetic patients' basal plasma triglyceride, total- and free- (unesterified) cholesterol, HDL cholesterol (HDL-chol), and apolipoprotein AI, AII, and B concentrations were similar to those of control subjects, but the free-cholesterol-to-lecithin ratio, a new index of cardiovascular disease risk, was significantly increased in their plasma (0.97 +/- 0.14 vs. 0.88 +/- 0.07, P less than .02) and their very-low-density lipoprotein (VLDL)-low-density lipoprotein (LDL) subfraction (1.50 +/- 0.51 vs. 1.08 +/- 0.15, P less than .005). Although HDL2-chol was similar in diabetic and control groups, the HDL2-chol-to-free-cholesterol ratio (diabetic vs. control, 4.64 +/- 1.7 vs. 1.96 +/- 1.0 mumol/ml, P less than .025) and the sphingomyelin-to-lecithin ratio (0.23 +/- 0.08 vs. 0.20 +/- 0.09, P less than .025) were both significantly increased in the IDDM group. HDL3-chol was higher in the IDDM than in the control subjects (diabetic vs. control, 38.6 +/- 5.2 vs. 32.7 +/- 2.7 mg/dl, P less than .005). In contrast to whole plasma and the VLDL + LDL subfraction, the free-cholesterol-to-lecithin ratio of IDDM and control HDL subfractions were similar.(ABSTRACT TRUNCATED AT 250 WORDS)