The first 2,013 fetuses in 2,000 patients undergoing genetic amniocentesis at our institution were analyzed for the incidence of abnormal findings and for the safety and accuracy of the procedure. One percent of the patients were found to have aneuploid fetuses and another 1% were found to have elevated amniotic fluid concentrations of alpha-fetoprotein. Advanced maternal age was the indication for amniocentesis in 84% of the women with aneuploid fetuses. Thirty-two (1.6%) of the pregnancies ended in spontaneous abortion and 35 (1.7%) were terminated because of abnormal results of the prenatal diagnostic procedure. Our error rate was 0.15%, and tissue culture was successful in 97.7% of the procedures. During the latter part of our experience concurrent ultrasonography was utilized with the amniocentesis, resulting in a reduction in blood-tinged specimens from 15.0% to 5.2%. In experienced hands, midtrimester amniocentesis for the purpose of prenatal diagnosis of genetically determined defects is a safe, accurate, and valuable procedure for the identification of fetal abnormalities.