Archived here for its historical relevance is this early publication of an extensive rationale for a multiple risk factor intervention trial of coronary disease prevention (MRFIT). It was written for a volume of invited editorials on Trends in Epidemiology published in 1972 by C.C. Thomas and edited by Gordon Stewart of Glasgow. It was based largely on the deliberations of 3 bodies of experienced researchers in CVD epidemiology and prevention trials: a U.S National Collaborative Group that had carried out a Pilot Trial of Physical Activity in the Prevention of CHD during the 1960s; The Makarska Conference on Mass Trials in the Prevention of Coronary Disease, convened by the International Society of Cardiology in September 1968; and The WHO Working Group on Multiple Risk Factor Intervention Trials of Prevention of Ischemic Heart Disease that met in Rome in October 1971. These deliberations and this article were central to the development of subsequent NIH and WHO research policy and program of CVD prevention (Henry Blackburn).