The granulomatous lesions in bovine paratuberculosis have been classified into 2 types, i.e. lepromatous type and tuberculoid type. Lepromatous type lesions are categorized as diffuse granulomas composed of many macrophages and epithelioid cells bearing large numbers of mycobacteria. Tuberculoid type lesions are categorized as focal granulomas consist of small numbers of macrophages and many lymphocytes with no or scant numbers of bicilli. In this study, we compared the cytokine gene expression between the two types of granulomatous lesions in ileal tissues. Ileal samples were obtained from noninfected control cows (n = 5: noninfected group) and infected cows (n = 6) that were diagnosed by ELISA or fecal culture test, and were processed for RT-PCR and in situ hybridization to detect cytokine mRNAs. All of infected cows were in the early stages of disease without clinical signs, and the tuberculoid lesions were observed in 4 cows (tuberculoid group) and the lepromatous lesions were in 2 cows (lepromatous group). Among cytokines examined, interleukin-2 (IL-2) and Th2 type cytokines, IL-4 and IL-10, were expressed more in lepromatous group than that in tuberculoid group. The expression of IL-12, however, was not different among the two groups and noninfected group, yet IL-18 was expressed lower in the lepromatous group than that in the tuberculoid group and noninfected group. In addition, IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) were expressed more in the lepromatous group than that in the tuberculoid group. On the contrary, expression of Th1 type cytokine, interferon-gamma (IFN-gamma), was more in the tuberculoid group than that in the lepromatous group. These results indicate that the formation of lepromatous lesions or tuberculoid lesions may be influenced by alterations in Th1/Th2 type cytokine production, and IL-18 may play an important role in a Th1 to Th2 switch.