From November 1991 through March 1992, we evaluated 101 free-ranging American bison (Bison bison) from Yellowstone National Park, Wyoming (USA) for exposure to infectious organisms that commonly infect cattle. No titers were detected for bluetongue virus, bovine leukemia virus, or Campylobacter fetus in these 101 bison. Detectable antibodies occurred against Anaplasma marginale (eight of 76, 11%), bovine respiratory syncytial virus (31 of 101, 31%), bovine viral diarrhea (31 of 101, 31%), bovine herpesvirus 1 (29 of 76, 38%), Leptospira interrogans icterohaemorrhagiae (four of 101, 4%), L interrogans hardjo (seven of 101, 7%), L interrogans autumnalis (one of 101, 1%), L interrogans bratislava (seven of 101, 7%), L interrogans australis (one of 101, 1%), and parainfluenza 3 virus (27 of 75, 36%). The low antibody titers and the lack of gross lesions are evidence that while previous exposure to infectious organisms may have occurred, none appeared to have active infections.