Antibodies are disclosed which specifically bind to native PrP.sup.Sc in situ. Preferred antibodies bind only to the native PrP.sup.Sc of a particular species e.g., human, cow, sheep, pig, etc. Particularly preferred antibodies bind specifically to a particular isoform of human PrP.sup.Sc. Preferred antibodies of the invention are (1) produced by phage display methodology, (2) bind specifically to native PrP.sup.Sc, (3) neutralizes the infectivity of prions, (4) bind to PrP.sup.Sc in situ and (5) bind 50% or more of PrP.sup.Sc in a liquid flowable sample. Antibodies of the invention can be bound to a substrate and used to assay a sample (which has any PrP.sup.c denatured via proteinase K) for the presence of PrP.sup.Sc of a specific species which PrP.sup.Sc is associated with disease. Antibodies which specifically bind to human PrP.sup.Sc can be labeled and injected carrying out an in vivo diagnostic test to determine if the human is infected with prions associated with disease. The antibodies are preferably produced using phage display technology wherein the genetic material in the phage expressing the antibody is obtained from a mammal with an ablated endogenous PrP protein gene and an endogenous chimeric PrP gene which mammal had been inoculated with PrP.sup.Sc to induce antibody production.