56 women who had had proteinuric pre-eclampsia and who had parous sisters were studied. In first pregnancy, proteinuric pre-eclampsia was more common in the sisters than in the maternity hospital population (8/71 [11%] vs 41/1978 [2%]); the relative risk was 6.0. The frequency of HLA DR4 was higher in sisters with pregnancy-induced hypertension than in sisters with normotensive pregnancies (8/18 [44%] vs 10/54 [19%]) and more of them shared HLA DR4 with their spouses (4/14 [29%] vs 0/29). Genetic susceptibility to pre-eclampsia is associated with HLA DR4; it may be conferred by fetomaternal sharing of a single recessive HLA-linked gene.