Recent works have shown some coding and non-coding polymorphisms of the NRAMP1 gene altering susceptibility to M. tuberculosis and other intracellular pathogens in mice and humans. In cattle, NRAMP1 gene is a major candidate gene controlling natural resistance to brucellosis, but it has been shown recently that under field conditions it does not determine resistance or susceptibility to M. bovis. However, no data is available regarding paratuberculosis. Here, we present a case-control preliminary study in a naturally infected herd where the potential correlation of 3 polymorphic markers for the NRAMP1 gene with susceptibility or resistance to Johne's disease were investigated by comparing the distribution of frequencies of several polymorphims in a sample of 44 ELISA positive and 100 ELISA negative cattle. Only one polymorphism at the 3'-UTR microsatellite showed a different frequency between the two groups. The GT11 allele had a frequency significantly higher in the seronegative (0.22) than in the seropositive (0.07) group. Since ELISA has a low sensitivity and a detectable humoral immune response is closely related to the development of clinical disease, these results suggest that NRAMP1 is involved in lesion progression. Further research is needed to evaluate the effects of this genetic condition on the pathogenesis of paratuberculosis and, therefore, to determine whether genetic selection can be of practical value for control of paratuberculosis.