Johne's disease, caused by Mycobacterium avium, subspecies paratuberculosis (MAP) is becoming increasingly widespread on dairy farms worldwide, due in part, to the absence of vaccine/drug or curative modalities. This spread is of concern since MAP is at the center of a controversy as to its role in Crohn's disease. None of the methods presently available to define paratuberculosis in cattle have been examined for their ability to assess progression/regression of any treatment or intervention of this disease The research presented herein, therefore was designed to assess the reliability and accuracy of available ante-mortem assays to predict disease change of individual animals undergoing a probiotic, potentially therapeutic, treatment. Paratuberculosis positive (n = 75) and negative (n = 10) animals were longitudinally monitored over their natural lifetimes with specific serum antibody and fecal shedding assays, and for development of end-stage clinical disease. Longitudinal, increasing/decreasing serum ELISA values were associated with, and predictive of, progression/regression of disease. Changes in fecal shedding and serum AGID were of value at only specific stages. Documentation that ELISA-positive animals were positive for paratuberculosis was done by a compilation of ELISA-independent assays--succumbing with end-stage clinical disease, autopsy, AGID, and MAP fecal shedding.