Abstract : In 1979 the United States Air Force (USAF) made the commitment to Congress and to the White House to conduct an epidemiologic study of the possible health effects from chemical exposure in Air Force personnel who conducted aerial herbicide dissemination missions in Vietnam (Operation RANCH HAND). The purpose of this epidemiologic investigation is to determine whether long-term health effects exist and can be attributed to occupational exposure to herbicides. This study uses a matched cohort design in a noncurrent prospective setting incorporating mortality, morbidity, and followup studies, Detailed computer searches of Air Force personnel records, with several cross-referencing techniques, have ensured total ascertainment of the RANCH HAND population. The unique circumstances of exposure in this population of 1264 individuals will permit a semiquantitative estimate of exposure. A comparison group will be formed from a population of 23,978 flight crew members and support personnel who were assigned to duty in Southeast Asia (SEA), but were not occupationally exposed to herbicides. These individuals will be matched to RANCH HAND personnel for the variables of age, type of job, and race. Since both the exposed subjects and their selected controls performed similar combat or combat-related jobs, many of the physical and psychophysiologic effects of combat stress and the SEA environment will also be equivalent in the two groups.