Serum inhibin A and activin A concentrations increase in pre-eclampsia. We investigated the time courses of the changes in relation to the onset of the maternal syndrome and if their measurement could be useful for clinical prediction particularly in relation to early onset disease, the most severe of the clinical presentations. Serial samples were taken from 1496 healthy nulliparae. Changes in activin A and inhibin A were analysed in women with: early onset pre-eclampsia (n = 11), pre-eclampsia delivering at 34-36 weeks (n = 14), term pre-eclampsia (n = 25) and gestational hypertension (n = 25); and in a subset with uncomplicated pregnancies (n = 25). Serum inhibin A and activin A were increased in all groups prior to pre-eclampsia, before 20 weeks in those with early onset pre-eclampsia. Screening efficacy was determined at 15-19 and 21-25 weeks in all women who developed pre-eclampsia (n = 70) and randomly selected controls (n = 240). Predictive sensitivities were low (16-59%) but much better for early onset pre-eclampsia: 67 and 44% at 15-19 weeks and 89 and 89% at 21-25 weeks for inhibin A and activin A respectively. Hence, serum inhibin A and activin A concentrations increase before the onset of pre-eclampsia at gestational ages that depend on when pre-eclampsia develops. On their own such measures are unlikely to prove efficient for screening.