Patients with diabetes mellitus often exhibit abnormalities in plasma lipoprotein concentrations. We have examined the effect of glycemic control (as assessed by hemoglobin A1 levels) on the concentrations of plasma lipoproteins and apoproteins in 109 patients with type I diabetes mellitus. HbA1 levels showed positive correlations with plasma LDL-cholesterol levels (r = 0.31; P < 0.002) and triglyceride levels (r = 0.41; P < 0.002), but not with HDL-cholesterol levels. The strongest correlation was between HbA1 and plasma levels of apoprotein B (r = 0.57; P < 0.001). We have also examined the effect of long-term improvement in glycemic control (achieved with insulin infusion pump therapy) on plasma lipoproteins in six patients with type I diabetes. Patients were followed for 5 to 12 months, with mean (± SD) HbA1c levels decreasing from 11.4 ± 2.5 to 9.1 ± 1.8. Most, but not all, patients showed reduction in plasma LDL-cholesterol levels and increase in plasma HDL-cholesterol levels, but these did not reach statistical significance. Only the decrease in plasma apo B levels was statistically significant (from 112 ± 38 mg/dL before pump therapy to 91 ± 33 mg/dL at the end of the follow-up, P < 0.05). We conclude that glycemic control plays an important role in regulating the levels of plasma LDL-cholesterol and triglycerides in patients with type I diabetes. Apoprotein B is a particularly sensitive indicator to alterations in glycemic control. It is possible that tight glycemic control may have "antiatherogenic" effects through reduction of apo B levels.