Osteogenesis Imperfecta (OI) is an hereditary disease of connective tissue, characterised clinically by frequent fracture following minimal trauma. Advances in molecular biology have demonstrated type I procollagen gene mutations in OI, this has not been matched by studies in the transmission electron microscope. The aim of this study was to investigate histological and ultrastructural changes of bone collagen and microanalytical changes of bone mineral in OI. Ultrastructurally, cellular changes were observed, possibly due to the poor secretion of abnormal type I procollagen chains. Fibrils were observed associated with type I collagen, possibly representing degraded collagen or abnormal collagen formed de novo. Histomorphometry of bone osteoid type I collagen fibre diameters, demonstrated larger diameter fibrils in OI compared to normal bone, possibly indicating an altered packing of collagen molecules. An X-ray microanalysis technique was developed, and determined the molar calcium to phosphorus (Ca/P) ratio of OI cortical bone to be lower than normal. Analytical studies on bone mineral suggested an apatite lattice was maintained, despite the possible ionic substitutions resulting in a low Ca/P ratio. A transgenic mouse with a mutated type I procollagen was investigated using the methodologies applied to human OI bone. Radiography and alizarin red staining demonstrated multiple fractures. Fibrils associated with type I collagen were observed. Analytical studies correlated well with OI data, a lower Ca/P ratio was observed in transgenic mouse bone. Molecular biological results have indicated that some mutations cause substitutions for glycine, this study has shown that these appear to alter the quarternary structure of the type I collagen. Alteration in collagen architecture may change the stereochemistry and hence the nucleation and growth environment for apatite. Also, an increased opportunity for ionic substitution and adsorption of ions may result. The findings of this study point to certain abnormalities in type I collagen and mineral formation and may be associated with the increased ease and frequency of bone fractures in OI.