OBJECTIVE: Our purpose was to evaluate second-trimester prenatal screening for open neural tube defects and Down syndrome by use of dried blood specimen collection and transport. STUDY DESIGN: A prospective study of 7497 dried blood specimens from patients <35 years old was performed. Specimens were assayed for maternal blood α-fetoprotein and free β-human chorionic gonadotropin. Patient-specific risks for both disorders were calculated and used to determine whether further evaluation was indicated. The study included an evaluation of the median and SD of analyte multiple of the median levels. RESULTS: The initial positive rate for open neural tube defect was 4.4% adjusted to 2.7% after ultrasonographic revision and collection of a second sample. The initial positive rate for Down syndrome was 3.6%, adjusted to 2.8% after ultrasonographic revision. All seven cases of open neural tube defect were detected within the increased risk group. Six of 8 (75%) cases of Down syndrome were detected. The median α-fetoprotein multiple of the median was 3.5 in open neural tube defect cases and 0.6 in Down syndrome cases. The median free β-human chorionic gonadotropin multiple of the median was 2.4 in Down syndrome cases. The SD (log_e) of α-fetoprotein and free β-human chorionic gonadotropin in 5868 unaffected white patients was 0.4022 and 0.5635, respectively. CONCLUSION: Second-trimester dried blood screening for open neural tube defects and Down syndrome can achieve screening efficiency comparable to serum-based protocols with distinct advantages over the conventional method of blood collection. (AM J OBSTET GYNECOL 1996;174:566-72.)