It has been suggested that gene aberrations may contribute to vascular endothelial dysfunction of pre‐eclampsia in Caucasian and Japanese women. This study was undertaken to examine the association between pre‐eclampsia in Black Zulu speaking South African women and the Factor 5 Leiden mutation. 100 patients with pre‐eclampsia comprised the study group. The control group comprised 110 normotensive pregnant women of the same population group. Genotyping was performed to detect the G or A allele at residue 506 of the Factor V gene, and the C or T allele at residue 455 of the thrombomodulin gene. Our findings demonstrate that these particularly genetic loci are of little use in disease association studies for pre‐eclampsia in homogenous Zulu speaking Africans.