Increasing evidence suggests that soil may serve as a natural reservoir of prion infectivity, thus In ruminants, scrapie and CWD, among the TSEs, can be horizontally transmitted via an environmental route, and by soil ingestion during grazing in particular Prions may enter the environment via by oral, nasal and skin secretions, urine, feces and parturient materials from both preclinical and diseased animals. Several in vitro studies suggest that after ingestion by ruminants, prions in contaminated soil seem resistant to rumen digestion and thus enter in the lower gastrointestinal tracts, where the infectious agents are up-taken across the epithelium and initiate infection along the lymphoid tissues and then in the CNS. It has been hypothesized that the odds of prion infection in free-ranging animals might be increased by high clay content in soil, but the contribution of soil humic substances (HS) (i.e. supramolecules able to polymerize and aggregate, forming micelles and supramolecular ensembles) in environmental TSEs has been so far neglected. Recent results showed that prions should be strongly retained in soil rich in organic matter, which would thus reduce the odds of infectivity among grazing lands. The anti-prion activity of HS might have an impact in reducing prion accessibility in the intestinal tract of animals, as well as in preventing the environmental transmission of TSEs among ruminants. To this purpose, we tested in vivo the ability of HS to reduce the prion accessibility in lambs. The animals have been divided into four groups: prionic protein administred per os (# 8, positive control), protein and humic substances per os (# 8), protein and humic substances via intragastrig gavage (# 8) and humic substances per os (# 4, negative control). The animals have been kept for 8 months; during this period they have been fed hey and feed. Afterwards, for each group, one animal has been sacrificed on a monthly basis (negative controls every two months), to investigate the diffusion of the prionic protein to the target organs. The following samples have been collected from each lamb: tonsils, thymus, viscera, SNC, nervous ganglia, lymph nodes) and tested through immunohistochemistry (IHC) and ELISA (IDEXX Herd Check BSE Scrapie - Antigen Test Kit). The preliminary results will be presented and discussed. This study has been financed by Ministery of Agricultural, Food and Forestry Policies (SCRASU Project)