This study traces the evolutionary pathways of the apolipoprotein B gene in the low risk Chinese and high risk Asian Indians in relation to coronary artery disease (CAD). Haplotypes were constructed from six apoB polymorphisms sp24/27, Ag(c/g), Ag(a1/d), XbaI, Ag(h/i) and, Ag(t/z). These were genotyped from 474 Chinese (253 healthy, 221 CAD patients) and 248 Asian Indians (164 healthy, 84 CAD patients). The maximum parsimony method was used to construct a cladogram for each ethnic group. Three haplotypes in the Chinese and one in the Indians were found exclusively in CAD patients. These haplotypes were sp27ca1X-ht, sp24ga1X-iz and sp24ca1X + it in Chinese, and sp24cdX-it in Indians. Those in the Chinese all occurred as terminal haplotypes and represented the most recent mutations. Evolutionary pathways for both ethnic groups were similar for majority of the haplotypes except for the presence of an additional third branch in the Indians arising from the ancestral haplotype. However, this third branch does not appear to contribute to the susceptibility of the Indians to CAD.