To understand the relevance of aerogenic transmission for bovine tuberculosis, it is important to study cattle experimentally infected with low doses of Mycobacterium bovis that result in pathology of the lower respiratory tract resembling that of most naturally infected cattle. In this study, we have compared and contrasted granuloma distribution and formation from cattle infected with low doses (1–1000 colony-forming units (cfu)) of M. bovis over 24 weeks. We also studied the expression of the cytokine IFN-γ in lymph nodes by immunohistochemistry (IHC) as well as by ELISA from in vitro-stimulated peripheral blood cells. Our results confirmed that 50% of cattle infected with only 1cfu of field strain (AF2122/97) M. bovis developed advanced granulomas in thoracic lymph nodes. The degree of lesion advancement and granuloma distribution was similar between the lowest dose group (1cfu) and the highest of the 4 groups (1000cfu). The number of acid-fast bacilli identified within the granulomas was also similar among all groups. IFN-γ expression was not significantly correlated with the infective dosage in either granuloma IHC or ante-mortem ELISA. These studies confirm that within the same time period, the smallest possible infective dose, properly administered, can produce pathology indistinguishable from a dose 1000-fold greater.