In U.S. white populations prenatal screening for cystic fibrosis can identify > or = 60% of pregnancies in which the risk for an affected fetus is high. Such pregnancies occur when both the mother and the father carry cystic fibrosis mutations; about one screened couple per 1000 falls into this category. The risk of the fetus being affected is 1 in 4. Prenatal screening for cystic fibrosis compares favorably with prenatal screening for spina bifida and Down syndrome, with a similar detection rate, a much lower false-positive rate, and greater odds of being affected, given a positive result. Intervention trials in Europe and the United States provide documentation of efficacy. Larger-scale trials should now be encouraged in the United States to gain further insight into program design and case management, as a way to determine the feasibility of cystic fibrosis screening as part of routine prenatal care.