Previous studies found that MZ twin pairs who are blood group NN have greater intrapair variability in plasma lipid levels than those who are MM or MN. This led to the prediction that the response of plasma lipid levels to a low fat diet would depend on MN blood group, the greatest response being in those who are NN. The present study was based upon 254 patients who took part in the Australian Polyp Prevention Project. This was a 2 x 2 x 2 randomised factorial design based upon the presence or absence of the three factors: a dietary fibre supplement, a beta-carotene supplement and reduced intake of dietary fat. The lowering of plasma, low density lipoprotein (LDL) cholesterol, in response to a low fat diet was greatest in those who were NN and least in MN heterozygotes. Overall, a reduction in LDL level was observed in the 47% of the APPP population who were on a low fat diet and who were homozygous MM or NN. The result was consistent with a balanced polymorphism at or near the GLYA locus on chromosome 4 that influences the sensitivity of plasma lipid levels to dietary fluctuations in fat intake.