The success of efforts to control bovine paratuberculosis depends on the early detection of infected animals, hereby allowing for removal of carriers. Recently, Wood et al. described an enzyme immunoassay for interferon- (IFN- EIA) as an in vitro assay for cell-mediate immune (CMI) response, which endowed excellent sensitivity in detecting subclinically infected animals. The object of this investigation was to evaluate the potential usefulness of INF- EIA as an early diagnosis of bovine paratuberculosis. At 4 to 5 days of age, 6 calf were inoculated orally with 500 mg of M. paratuberculosis and blood samples collected periodically for 12 months were subjected to the INF- EIA, the lymphocyte-transformation (LT) test. These animals began fecal shedding at 3 to 4 months after the inoculation and remained so throughout the study. Positive results in INF- EIA an LT test were obtained 2 to 4 months after inoculation. The magnitude of the CMI response to johnin PPD was higher than that to bovine PPD. The INF- EIA titer (ng/ml) tended to remain at highly positive level more consistently than LT titer (stimulation index) in the animals. Positive conversion of ELISA antibody titer was detected 8 to 10 months after the inoculation. The results have substantiated the profile of immunological response of paratuberculosis that CMI response precede humoral immune response, and also indicate that INF- EIA may become a useful tool for the early diagnosis of subclinical paratuberculous cattle.