To investigate the effects of oral administration of an interferon (IFN)-alpha drug on the immune reaction of healthy Japanese Black (JB) calves, peripheral leukocyte populations and their ability to produce cytokine mRNA were analyzed after oral administration of IFN-alpha. Fourteen calves fed in one herd were divided into two groups; seven calves were orally administered 0.1 g/day of IFN-alpha from the day of birth to day 5 on each day (group 1, N=7), and the other seven calves were used as the control (group 2, N=7). Blood samples were collected from the jugular veins of all calves before administration and in weeks 1, 2, 4, 8, and 16 after birth. The number of MHC class II+CD14+ monocytes in the leukocytes population of group 1 increased gradually after birth, and significantly higher numbers were detected in week 4 compared with group 2. MHC class II-CD14+ monocytes in group 1 peaked in week 1, and a significant increase was detected compared with group 2. The level of IL-12 in the cytokine mRNA of group 1 increased gradually between weeks 1 and 2, and a significantly higher level of IL-12 was found compared with group 2. These results suggest that oral administration of IFN-alpha induces activation of the monocyte functions in JB calves.