BACKGROUND: Differences in serum lipid distribution and mortality from ischaemic heart disease have repeatedly been reported between Belgian northerners and southerners. We investigated whether serum lipoprotein(a) (Lp(a)) and apolipoprotein (apo) E polymorphism were involved. METHODS: Fasting serum lipids, apo A-I and B, and Lp(a) levels were examined in randomly selected, 20-39 year old Belgian males and females from the north (Flanders) and the south (Wallonia) of Belgium (N = 900). Apo E phenotype distribution was investigated in random subsamples from either region (N = 249). RESULTS: Mean serum cholesterol, low density lipoprotein cholesterol (LDL-c), apo B and triglyceride levels were higher in Walloons compared to Flemings within each gender, the difference being significant in 30-39 year old males. Average high density lipoprotein cholesterol and apo A-I levels were significantly lower in 30-39 year old male southerners, compared to their northern counterparts. Median Lp(a) was 67 mg/l in northerners and 75 mg/l in southerners (NS). The apo E phenotype distribution was similar in both regions (chi2 = 7.213; d.f. = 5; P = 0.2053), whereas the average effects of the apo E alleles differed between the regions. In southerners the epsilon4 effect upon adjusted apo B and LDL-c levels was approximately+12% and the epsilon2 effect was approximately-15%; in northerners the epsilon4 and epsilon2 effects were approximately+5% and approximately-25%, respectively. The apo E polymorphism did not affect serum Lp(a) levels. CONCLUSIONS: Regional cholesterol differences between Flemings and Walloons cannot be explained by differences in serum Lp(a) or apo E phenotype distribution. The less favourable epsilon2 and epsilon4 effects in southerners compared to northerners reflect modulation of the apo E gene by particular environments.