The human skeletal collection of the National Museum of Natural History contains approximately 35,000 specimens from the major geographical areas of the world and representing a time depth of at least 5000 years. About 3,000 of the skeletons exhibit pathological conditions of special significance. These pathological cases represent a valuable source of data on the history of diseases involving the skeleton. They also offer the opportunity of studying more completely the expression of skeletal disease in largely untreated cases and at various stages in the skeletal manifestations of disease. Careful study of such specimens also reveals features that are important for a fuller understanding of the pathogenesis of many diseases affecting the skeleton. The focus of the proposed research will be on a selected sample (N = about 300) of these pathological cases that are of particular interest because of one or more of the following criteria: (1) the pathological features of a case have morphological or distributional patterns that are unusual or distinctive, (2) the case exhibits a relatively uncommon condition, (3) the characteristics of a specimen offer the possibility of new insight on the pathogenesis of a particular disease, (4) the specimen has considerable epidemiological significance, and (5) the specimen presents difficulties in differential diagnosis. The specimens to be studied have already been identified as part of an inventory of the entire skeletal collection. One of the secondary benefits of the research program will be making these specimens more accessible to the scientific community through the development and utilization of an improved catalog utilizing a computer-based records management system. Basic to the methodology of the research will be an emphasis on clarifying and developing diagnostic criteria applicable to gross dry bone specimens. This will involve the careful study of the gross and roentgen morphology of each case and the attempt to explore additional criteria such as the fine structure (utilizing both light and scanning electron microscopy) of cancellous bone in various affected areas of the skeleton. Anticipated publication plans include the preparation of an annotated atlas of most of the 300 specimens which constitute the focus of the research. This research should enrich medical knowledge of the skeletal manifestations of disease, broaden understanding of the pathogenesis of skeletal disease, and provide additional data on the history, geographical distribution, and time depth of many human diseases.