Alpha-fetoprotein (AFP) was 1 of the first serum protein markers to serve in the dual capacities of tumor marker and fetal defect marker, ie, an oncofetal protein, in the clinical laboratory. Although the serum-marker capacity of AFP has long been used, less is known of the fluid compartments of this oncofetal protein during fetal and perinatal development. In this review, the biologic activities of AFP are discussed in light of its presence in the various biologic fluid compartments: fetal serum, amniotic fluid, cord blood, urine, and maternal serum. AFP concentrations within the biologic fluids are considered in the context of gestational age, sex, body weight, and anatomic location. Discussion follows concerning the relationships and roles of AFP in various developmental disorders such as hypothyroidism, folate deficiencies, autoimmune disorders, acquired immunodeficiency disorder (AIDS), congenital heart defects, cystic fibrosis, preeclampsia/hypertension, and platelet aggregation disorders. Based on its presence in so many types of birth defects, malformations, and congenital anomalies, AFP can be seen to serve as a form of molecular "duct tape" during pregnancy and postnatal development.