Objective To compare the prevalence of the Factor V Leiden mutation in children and maternal-infant pairs in pregnancies affected by severe pre-eclampsia with unmatched normal controls. Design Prospective cohort study. Setting Department of Women's and Children's Health, The Canberra Hospital, Garran, ACT, Australia. Sample Forty-eight maternal-infant pairs where the index pregnancy was affected by severe pre-eclampsia; 46 unmatched maternal-infant pairs where the index pregnancy was defined as normal. Methods DNA analysis of cheek swab samples obtained from maternal-infant pairs for the Factor V Leiden mutation. Main outcome measure The prevalence of the Factor V Leiden mutation in mothers, infants and maternal-infant pairs in association with severe pre-eclampsia compared with unmatched controls. Results No difference was detected in the prevalence of Factor V Leiden mutation between the women and children of both groups, nor the maternal-infant pairs from each group. Conclusions No evidence was found of an increased prevalence of the Factor V Leiden mutation in either the mothers or children in association with severe pre-eclampsia. This result argues against a Factor V Leiden fetal or maternal contribution to the development of severe pre-eclampsia.