Technical Abstract: Scrapie is a naturally occurring prion disease causing fatal neurodegenerative disorders in sheep and goats. PrP-Sc, the presumed causative agent for scrapie, accumulates in brain, lymphoid and placental tissues in sheep. PrP-Sc is derived from the normal isoform of PrP, PrP-C, which as the substrate for conversion to PrP-Sc is necessary for scrapie infection. Natural transmission of scrapie may be primarily through the reproductive tract and fetal-placental tissues/fluids. The objective of this study was to characterize the distribution and biochemical properties of PrP-C in female reproductive, fetal and placental tissues and fetal fluids of normal sheep. The results showed that PrP-C was present in endometrium, myometrium, oviduct and ovary of both pregnant and non-pregnant ewes and cotyledonary chorioallantois, allantoic fluid and fetal bladder. PrP-C was not detectable in the intercotyledonary chorioallantois, amnion, urachus, amniotic fluid, or fetal urine. PrP-C in allantoic fluid and the tissues was glycosylated, N-terminally truncated and proteinase K sensitive. These results are important to a further understanding of scrapie transmission through the reproductive processes and the physiological role of PrP-C in reproduction.