Bovine respiratory disease complex (BRD) consists of a largely single clinical entity of bronchopneumonia that is usually associated with the assembly of large numbers of especially weaner cattle into a feedlot environment. It has a multifactorial aetiology and develops as a result of complex interactions between environmental factors, host or animal factors and pathogens. It is often difficult to determine the exact role played by the various pathogens involved in an individual outbreak of disease. None of the many organisms isolated will on their own, reliably reproduce the natural disease in experimental animals. Observations from research studies and clinical experience have indicated that the presence of mycoplasmas increases the severity of respiratory disease. However, the role of Mycoplasma spp. in BRD complex as a primary or secondary pathogen remains controversial. The various stresses associated with the feedlot causes a breakdown of the defense mechanisms that normally hold the nasal infections in check, resulting in a rapid proliferation of virulent Mannheimia haemolytica serotype A1 in particular and the spread to the lower respiratory tract. The various viruses and mycoplasmas have however been shown to have the same effect as stress on the Pasteurella populations of the nasal mucosa. More than 10 species of Mycoplasma have been isolated from the bovine respiratory tract, but not all are pathogenic. They are able to act as a stress-causing agent, leading to a decreased host defense mechanism by altering the immune responsiveness or by causing tissue damage and thereby allowing bacteria to invade and colonise the lung and so causing a severe pneumonia. M. bovis and M. dispar are the more important lung isolates, with M. bovis being the most invasive and destructive and has been shown to increase the severity of calf pneumonias. M. bovis has been isolated from bovine pneumonias, arthritis, mastitis, tendosynovitis, genitalia, keratoconjunctivitis and is considered to be the primary pathogen in endemic pneumonia in younger calves. According to the literature, mycoplasmas are isolated from 25% to 80% of pneumonic lungs in feedlot cattle and the aim of the study was to identify the isolation rates in South African feedlots over a period of 2000 to 2004. To achieve this, 446 transtracheal aspirates (TTA’s) were collected from more than 25 feedlots around South Africa, except for the western Cape. Collection criteria included: pulled for respiratory disease; febrile (≥40ºC); depressed; anorexia and/or lack of rumen fill; nasal discharge or failure to clean muzzle; cough; increased respiratory rate >40 and most importantly, no prior treatment. Samples were also collected from 31 ‘healthy’ animals as controls. Samples collected were used for Mycoplasma isolations, as well as the aerobic bacteria to establish an antibiogram profile of bacteria commonly isolated in cattle feedlots. Mycoplasma spp. were isolated from 52.8% of samples taken from sick animals, with 67 out of 201 isolates (33.3%) being identified as M. bovis. According to the literature, M. bovis, M. haemolytica or P. multocida are isolated from bronchial lavage fluids from healthy calves in only a few cases, with estimates being put at 5 – 10% levels for Mycoplasma. Isolation rates of Mycoplasma spp. from healthy animals in this study was 22.7%, which was considerably higher than anticipated and could possibly be due to problems with the definition of a healthy animal. Although the number of samples from healthy animals was relatively small in this study, it was possible to show that there was a statistically significant association between Mycoplasma isolation and respiratory disease, p = 0,001 and with an odds ratio (OR) of 3,75 in cattle from those feedlots included in the study and thereby proving the hypothesis put forward.