Paratuberculosis, caused by Mycobacterium avium subsp. paratuberculosis (Map), is manifested by a broad spectrum of clinical and lesional presentations. We have evaluated the expression of transforming growth factor-beta1 (TGF-beta1), a cytokine known to have immunosuppressor effects, by immunohistochemistry, in different paratuberculosis lesions in the intestine and lymph nodes from 20 sheep and 25 cattle. Peripheral immune responses were assessed by interferon-gamma (IFN-gamma) test and the presence of antibodies. Expression of TGF-beta1, observed in macrophages and giant cells forming the lesions, was closely related to the amount of Map. In focal and multifocal forms, usually positive to IFN-gamma test, bacilli were difficult to detect and TGF-beta1 expression was low or absent. Diffuse multibacillary lesions, negative to IFN-gamma, show large numbers of Map and the highest percentage of immunolabelled cells. Diffuse paucibacillary forms, positive to IFN-gamma, have low numbers of AFB and scant or no cells positive to TGF-beta1. The high expression of TGF-beta1 would be related to the inability of macrophages to limit the multiplication of Map.