The purpose of this retrospective study was to determine if maternal serum (MSAFP) or amniotic fluid (AF-AFP) αfetoprotein analysis might he useful in detecting fetal structural defects in the first trimester. During a 5-year period, 20 fetal anomalies were diagnosed at 11-13 weeks by transvaginal ultrasound scanning. A MSAFP sample was obtained in all 20 patients and 17 patients had AF-AFP results obtained by an early amniocentesis. Ten of 20 patients (50% had elevated MSAFP levels, and 6 or 17 patients had elevated AF-AFP samples (35% MSAFP was elevated in 4 of 5 cases of anencephaly (80% in one fetus with the combined malformations of anencephaly and omphalocele, in one fetus with a large encephalocele, in 2 of 3 fetuses (67% with an omphalocele, and in two cases of cystic hygroma with an abnormal karyotype. AF-AFP was elevated in 3 of 3 cases of anencephaly, in one fetus with the combined defects of anencephaly and omphalocele, in 1 of 3 cases (33% of omphalocele, and in one fetus with an encephalocele. Our study suggests that MSAFP and AF-AFP analysis may prove useful in detecting fetal malformations in the first trimester. Larger prospective studies are needed to evaluate further the association of fetal anomalies and first-trimester AFP analysis. © 1995 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.