Pathogenesis studies of experimentally produced sheep-associated malignant catarrhal fever (MCF) in laboratory rabbits are described. Animals were examined at intervals after inoculation. The principal change was a proliferation of lymphoid cells which began as soon as three days and became quite pronounced by 13 days after inoculation. The appendix, mesenteric lymph node and spleen were most obviously affected. The reason for this was a progressive increase in T-lymphocytes, which appeared to be a hyperplasia rather than neoplasia in T-dependent areas of these organs. Lymphoid cells also accumulated in interstitial spaces of non-lymphoid organs. The use of cyclosporin-A suppressed the lymphoid proliferation but rabbits still developed clinical MCF after a similar incubation period. It is suggested that the agent of MCF might produce its effect by infecting and causing a dysfunction of lymphoregulatory cells, resulting in benign polyclonal T-lymphocyte proliferation. Terminal necrosis could be due to natural killer cell activity.