Abstract: Cross reactivity of three antigens of Mycobacterium avium subspecies paratuberculosis with sera of sheep endemic for Johne’s disease was evaluated. Out of 40 sheep tested by fecal microscopy, 72.5% were shedding MAP. Using protoplasmic antigens (PPA) from three MAP strains isolated from different livestock species and geographical regions, 90, 77.5 and 2.5% sheep were positive in goat (Indigenous g-ELISA) and cattle (b-ELISA) based ELISA kits and ELISA kit for small ruminant (sr-ELISA), respectively. Only 2.5 and 10% sheep were positive and negative in all the four tests. Native species specific (goat origin novel ‘Indian Bison Type’ MAP) semi-purified whole cell PPA based ELISA (Indigenous g-ELISA) was superior in reacting with sera of native sheep than the commercial PPA of bovine origin (Allied Monitor Inc., USA) and commercial ELISA kit for small ruminants (ID Vet, France). Lower cross reactivity of antigens originated from US and France emphasized the need to develop tests based on local strain of MAP than strains from different livestock species and geographical regions. This is an important finding against the use of ‘Global kits’ without validating in local conditions. Study showed that kits developed from local strains of MAP were not only superior but also cost effective and will significantly contribute in programs for the control of JD in native sheep population.