The possible spread of Mycobacterium paratuberculosis via blood monocytes throughout the body was studied. In addition, the distribution of M. paratuberculosis was examined by testing various tissues by PCR. Blood and fecal samples were taken twice a week from five clinically diseased cows. Blood samples were tested directly by PCR and also after first culturing the macrophages. From four cows, blood samples were positive by PCR either directly or after culturing the macrophages. The cows were autopsied and the spread of M. paratuberculosis throughout the body was studied by testing various tissues of these animals by PCR. Not only the intestinal tract but several non-intestinal tissues were positive for M. paratuberculosis DNA, indicating that paratuberculosis is a generalized infection, spread by infected peripheral blood macrophages. To study the potential to diagnose paratuberculosis directly in blood by PCR, blood samples of an infected dairy herd were tested. Fecal samples of three animals were cultured for confirmation. Blood samples of 60% of the animals were positive by PCR, whereas only 30% of the animals were shedders. The implications of this test for the early detection of infected animals are further studied.