Prion diseases, such as variant Creutzfeldt-Jakob disease (vCJD) in humans, scrapie in sheep and goats, and chronic wasting disease in deer and elk (CWD), follow a clinically silent phase of infection lasting between 2 and 50 years and progress relatively rapidly once neurologic signs appear. During the long silent phase of these infectious disorders, the pathogenic prion protein, PrPSc, accumulates in lymphoid tissues prior to invading the central nervous system. The key lymphoid reservoir for the disease-associated PrPSc is the follicular dendritic cell (FDC), a cell induced and maintained through lymphotoxin (LTa and LTb) and tumor necrosis factor (TNF) signalling from B cells. Recently, it was shown that inflamed organs containing follicular dendritic cells accumulate infectious prions in the mouse scrapie model. Here we propose to investigate: (1) whether a mastitic mammary gland harbors infectious prions in scrapie infected sheep, (2) whether milk from these sheep can transmit scrapie to uninfected lambs, and (3) whether a transgenic mouse with lymphoid follicular mastitis can be used to model scrapie transmission via milk to the mouse pups. Mastitic milk may serve as a conduit for sheep scrapie transmission, a finding which would also have broad ranging implications for general prion transmission in body fluids from inflamed organs.