During a 22-month period, 6288 women undergoing prenatal sonographic studies in the second and third trimesters were evaluated prospectively to determine the incidence of choroid plexus cysts in the fetus, to follow the natural course of these cysts in intrauterine life, and to determine the association of chromosomal and anatomic anomalies in these fetuses. We diagnosed choroid plexus cysts in 41 fetuses, an incidence of 0.65%. Unilateral and bilateral cysts were equally frequent, and in most cases diagnosed by 21 weeks' gestation. On follow-up scans, the cysts had completely disappeared by 23-24 weeks in 80% of the cases, and by 28 weeks in another 10%. Once resolved, the cysts did not recur, and a normal sonogram in the late second trimester predicted normal scans in late pregnancy and in the neonate. One fetus had a chromosomal abnormality (trisomy 18). Associated anatomic anomalies were detected in three fetuses, including the one with trisomy 18. We believe that in the great majority of cases, fetal choroid plexus cysts are benign transient variants of normal intracranial anatomy. It is, however, important to conduct a careful sonographic search for associated anomalies. Chromosomal studies are strongly recommended whenever associated anatomic abnormalities are detected and when the choroid plexus cysts are large, bilateral, and persistent beyond 20-22 weeks' gestation.