Concentrations of pregnancy-specific beta 1-glycoprotein (SP-1) were measured in maternal blood and amniotic fluid of patients with a trisomic fetus and compared with that of a cytogenetically normal fetus at weeks 16-19 of pregnancy. The SP-1 concentrations were significantly elevated in the sera of women with a Down's syndrome fetus, whereas amniotic fluid levels were only slightly increased. It is suggested that high levels of maternal SP-1 in the second trimester of pregnancy may be a valuable indicator in the prenatal detection of fetal trisomy 21.