Large amounts of amniotic fluid (AF) are swallowed in late gestation. AF is the most accessible fetal compartment and provides a possible paraplacental route for the therapeutic administration of hormones and nutrients to the fetus. We therefore wished to investigate the fate of the predominant fetal growth factor, IGF-I, administered into AF of late-gestation ovine fetuses. Seven chronically catheterized fetuses at 124 d gestation had approximately 800 x 10(6) dpm of (125)I-IGF-I injected into the AF. AF and blood samples were withdrawn for up to 6 d. At 131 d gestation a postmortem examination was performed. All AF, blood, and tissue samples were counted. Selected samples of AF, blood, and gut contents underwent size-separation chromatography. (125)I-IGF-I was rapidly mixed in AF, with a significant difference in counts from different regions of the cavity persisting for only 3 h (p < 0.05). In vivo binding of (125)I-IGF-I in AF correlated highly with AF IGF binding protein 3 concentrations (r(2) = 0.93, p < 0.0001). In some animals, free (125)I-IGF-I persisted in AF and in plasma for the duration of the experiments. Chromatography of plasma samples demonstrated that intact (125)I-IGF-I was taken up from the fetal gut. Only fetal gut and thyroid contained appreciable counts at postmortem examination. Gut contents had more counts than gut wall, and the number of counts in gut contents increased distally (p < 0.05 for colon contents versus other regions). We conclude that there is sustained delivery of (125)I-IGF-I from the AF to the gut and systemic circulation of the ovine fetus after a single intraamniotic injection.