In order to study the lipoprotein pattern in diabetes mellitus, plasma lipoproteins were isolated by rate zonal centrifugation in 12 control subjects (median fasting blood glucose level: 80 mg/dl (range: 74–86)), 14 diabetic patients treated by diet alone 104 mg/dl (76–153), 27 patients treated by diet plus insulin (180 mg/dl (106–404)), and 32 patients treated by diet plus sulphonylurea [178 mg/dl (103–361)]. No significant differences of median relative body weight existed between the four groups. Neither the diabetic group on diet alone nor the insulin-treated group differed significantly from control subjects with respect to lipid and lipoprotein concentrations. Diabetics treated with diet plus sulphonylurea, however, differed significantly from the control group with regard to the following parameters (median and range); plasma triglycerides (210 [75–620) mg/dl; p<0.01)] and intermediate density lipoproteins (65 (10–338) mg/dl; p<0.05)) were higher; low density lipoproteins (236 (82–418) mg/ dl; p<0.05)) and high density lipoproteins₂ (HDL₂) [51 (12–121) mg/dl; p<0.01)] concentrations were lower. When data from all 85 studied individuals were analysed together, significant positive correlations were observed between fasting blood glucose and plasma triglyceride concentration (r = 0.28, p<0.01), and between fasting blood glucose and plasma very low density lipoproteins (VLDL) (r = 0.23, p<0.05). A negative correlation was found between blood glucose and plasma HDL₂ (r = -0.29, p<0.01). In addition, VLDL correlated negatively with HDL₂ (r = -0.89, p<0.001) but not with plasma HDL₃ concentration. It is concluded that the deranged lipoprotein metabolism in diabetes mellitus may be better controlled by insulin than by sulphonylureas.