To evaluate the variations and potential clinical use of serial maternal alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) in pregnancies at risk of pregnancy-induced hypertension (PIH) andor intrauterine growth retardation (IUGR), we investigated the relationship between placental sonographic findings, uterine artery Doppler measurements, and maternal serum A m , hCG, and uric acid levels between 20 and 34 weeks of pregnancy. Maternal serum samples were collected from 41 singleton pregnancies with bilateral uterine notches andlor an increased uterine artery pulsatility index at 20-24 weeks. Maternal serum AFP, intact hCG and free a and j? subunits, and uric acid circulating levels were measured in all cases at 20-24 weeks and 25-28 weeks. Placental sonographic investigations comprised measurements of thickness and morphology. Twenty pregnancies had a normal outcome and 21 had an adverse outcome, including eight complicated by severe PIH with fetal IUGR, eight by isolated IUGR, three by mild PIH with normal fetal growth, and two by placental abruption. At the time of the first scan, the placental thickness and maternal serum levels of AFP, hCG, and uric acid were significantly increased in pregnancies with adverse outcomes, compared with those with a normal outcome. In subsequent maternal serum examinations, the incidence of elevated hormonal levels fell for AFP, intact hCG, and j?-hCG, whereas it increased for the uric acid level. No difference was found at any stage for the a-hCG level. Seven out of 11 pregnancies complicated by PIH presented with elevated MSAFP and MShCG and a large heterogeneous placenta at the first visit, whereas no pregnancy with a normal outcome presented with similar features. This study has shown a significant association between abnormal development of the utero-placental circulation, elevated MSAFP and MShCG at mid-gestation, and subsequent adverse pregnancy outcome. Serial measurements of MSAFP and MShCG do not provide extra information for the follow-up of these pregnancies.