Of all Indian Health Service areas, the Aberdeen Area has consistently had the highest infant mortality rate. Among some tribes in this area the rate has exceeded 30/1000 live birth and half the infant deaths have been attributed to Sudden Infant Death Syndrome, a rate four to five times higher than the national average. The Indian Health Service, Centers for Disease Control and Prevention, National Institute of Child Health and Human Development, and the Aberdeen Area Tribal Chairmen's Health Board collaborated to investigate these high rates with the goals of refining the ascertainment of the causes of death, improving cause-specific infant mortality rates and identifying factors contributing to the high rates. Ten of the 19 tribes or tribal communities, representing 66% of the area population, participated in a 4-year prospective case-control study of infants who died after discharge from the hospital. Infant care practices and socio-demographic, economic, medical, health care, and environmental factors were examined. The study included parental interviews, death scene investigations, autopsies, neuropathology studies, medical chart abstractions, blood cotinine assays, and a surveillance system for infant deaths. Controls were the previous and subsequent infants born on the case mother's reservation. From December 1, 1992 until November 30, 1996, 72 infant deaths were investigated. This report describes the study methods and the model employed for involving the community and multiple agencies to study the problem of infant mortality among Northern Plains Indians. Data gathered during the investigations are being analyzed and will be published at a later date. The following is appended: (1) Reduction of Infant Mortality Recommendations for Parents. [This study is also supported by the Centers of Disease Prevention and Control (CDC) and the Tribal Chairmen's Health Board (AATCHB).] (Contains 2 tables.)