Acute hyperinsulinemia lowers plasma apolipoprotein B (apo B) and triglycerides by suppressing hepatic lipoprotein secretion and probably by enhancing catabolism of triglyceride-rich lipoproteins, but the effect of acute hyperinsulinemia on the plasma lipoprotein(a) (Lp(a)) level is unclear. We measured plasma triglycerides, cholesterol, apo B and Lp(a) in response to 3 h hyperglycemia-induced hyperinsulinemia (blood glucose clamped at 10 mmol/l) in 16 subjects (eight women and eight men). In a control experiment saline was infused in another group of seven men. After 3 h of hyperinsulinemia plasma triglycerides decreased by 29 +/- 14% (mean +/- S.D., P < 0.001) and this fall differed from the unchanged triglyceride level during saline infusion (P < 0.001). Plasma cholesterol fell by 8 +/- 5% (P < 0.001), which was different from the unchanged cholesterol during saline infusion (P < 0.02). Plasma apo B decreased by 9 +/- 8% (P < 0.001), which was again different from the minor fall in apo B (3 +/- 2%) during saline infusion (P < 0.02). However, plasma Lp(a) remained unchanged during hyperinsulinemia (change 8 +/- 15%, n.s.), as well as during saline infusion (change 5 +/- 15%, n.s.). The % change in apo B exceeded the % change in Lp(a) during hyperinsulinemia (P < 0.01). Baseline Lp(a) was inversely correlated with first phase insulin secretion (P < 0.05), but its level during the clamp was not related to insulin sensitivity. This study demonstrates that acute hyperglycemia-induced hyperinsulinemia has a different effect on plasma apo B and Lp(a) in healthy subjects. The present data support the notion that Lp(a) is metabolized differently from triglyceride-rich lipoproteins.