There is interindividual variation in plasma lipid response to dietary changes. The polymorphisms which are associated with plasma lipid levels could possibly explain part of this variation. Therefore, the apolipoprotein B (apo B) signal peptide insertion/deletion (ins/del) and XbaI restriction fragment length polymorphisms are possible regulators of plasma lipid responses. We examined their role in the regulation of plasma lipid responses in 87 North Karelians (43 men, 44 women). The dietary study consisted of a 2-week baseline period (34-35% of energy from fat), followed by an 8-week low-fat (24 En%), low-cholesterol (279 mg/d) diet period and an 8-week switchback period. In this study population the apo B ins/del and XbaI polymorphisms exhibited mainly similar and partly significant effects on the responses of plasma very low-density lipoprotein (VLDL) and high density lipoprotein2 (HDL2) cholesterol to dietary changes. After consumption of the low saturated fat, low-cholesterol diet, ins/ins X - /X - homozygotes showed the greatest increase in VLDL cholesterol (p < 0.05 for differences between ins/del genotypes) and the greatest fall in HDL2 cholesterol (p = 0.01 for ins/del and p = 0.05 for XbaI), while only minimal alterations were seen in the del/del and X + /X + groups. After returning to the original diet, the changes of these lipids were reversed, ins/ins and X -/X - homozygotes having the greatest reductions in VLDL cholesterol (p < 0.05 for XbaI) and the greatest increases in HLDL2 cholesterol (p < 0.001 for XbaI). The findings suggest that plasma VLDL and HDL2 cholesterol responsiveness to diet may be partly explained by variation at the apo B gene.