This application is for support of an international conference on the mechanism of cell-mediated calcification with special emphasis on matrix vesicles which serve as the initial site of calcification in predentin, developing bone and growth cartilage. Calcification is a fundamental biological process, defects of which underlie many skeletal, dental and calcific diseases. Yet, the mechanism of calcification remains incompletely understood. The conference will assemble an international group of noted scientists, and will conduct a four-day program of presentations and discussions aimed at stimulating research in this area. The scope of the conference will be broad enough to attract scientists with a wide range of interests including the chemistry of bone mineral, the ultrastructure of mineralizing tissues, matrix macromolecules which play a role in mineralization (e.g. lipids, collagen, proteoglycans, calcium-binding matrix molecules and non-collagenous proteins), matrix vesicle membranes and constitutive proteins and enzymes which may promote initial mineralization, the regulation of matrix vesicle biogenesis, and calcific diseases. To foster greater personal interaction and the development of collaborative efforts, the meeting will follow a Gordon Research Conference-type of format with morning and evening sessions and afternoons largely free for informal discussions. Discussion will be further encouraged by limiting the number of papers per session and setting aside time at the end of each session. Poster sessions will provide wider coverage of recent research. Young scientists who submit outstanding abstracts will be considered for Young Investigator Awards, and for reporting their findings at an oral session. The conference is the fifth in a series of international meetings related to matrix vesicles and cell-mediated calcification of which two were held in the United States (1975, 1978), one in Italy (1981) and one in England (1985). It is timely that the conference return to the United States, under the sponsorship of the NIH, as it was in 1978. The central theme will be the broad topic of how cells ultimately control calcification, or lose control with devastating clinical effects upon the host.