A total of 681 pregnant women were referred for evaluation of elevated maternal serum alpha-fetoprotein levels. Ultrasonographic examination yielded an explanation for the elevation of maternal serum alpha-fetoprotein in 42% of patients. Diagnoses made by ultrasonography included incorrect fetal dating, multiple gestation, fetal death, open neural tube defect, abdominal wall defect, placental abnormalities, cystic hygroma, renal anomalies, and oligohydramnios. Optimal prenatal diagnosis of fetal anomalies also requires the use of amniocentesis in many patients. Amniocentesis may be obviated if fetal dating is incorrect, if an unsuspected multiple gestation is discovered, or if there is a clear anomaly and the parents do not desire genetic counseling based on karyotype information. If the fetus appears normal, the ultrasonographic results are equivocal, or the parents desire more detailed genetic counseling when an anomaly is found by ultrasonography, then amniocentesis should be performed. Thirteen abnormalities were diagnosed by amniocentesis alone in this group.