The objective of this study is to gain operational knowledge and mechanistic understanding of the mechanical and electrical effects of bone and cartilage growth and remodeling. Chick and rat bone, and cartilage, rudiments or cells, are exposed to controlled mechanical or electrical perturbations in tissue culture. We measure changes in cAMP cGMP accumulation and localization (immuno-histochemistry), Na ion and Ca2 ion fluxes, DNA synthesis, histological appearance (tetracycline labeling) and correlate the changes to the local perturbation (as calculated by computer analysis of stress distribution). Results obtained so far support the hypothesis that mechanical and electrical stimuli act on cell membranes, modulate ion fluxes (Ca2 ion, Na ion) and cyclic nucleotide levels (cAMP, cGMP) and affect DNA synthesis. Responsiveness to the stimuli depends on the state of cellular differentiation (tissue and cell type specificity) and is related to biochemical and biophysical properties of the cell membrane. BIBLIOGRAPHIC REFERENCES: Norton, L.A., G.A. Rodan and L.A. Bourret. Epiphyseal cartilage cAMP changes produced by electrical and mechanical perturbations. J. Orthop. Surg., in press, 1977. Rodan, G.A., L.A. Bourret and L.S. Cutler. Membrane changes during cartilage maturation: Increase in 5'-nucleotidase and decrease in adenosine inhibition of adenylate cyclase. J. Cell Biol., in press, 1977.