We evaluated the distribution of Type III collagen, Type VI collagen, and fibrillin in human bone, using monoclonal antibodies (MAb) of proven specificity. All three molecules are present in developing and remodeling bone. Type III collagen is present in discrete fiber bundles throughout the bone cortex but is concentrated at the Haversian canal surface and in the fibers at the bone-periosteal interface. The collagen fibrils in these bundles are of uniform diameter. Type III-containing collagen fibers are detected at all ages examined, from 30 fetal weeks to 80 years. Type VI collagen is present in fetal bone in discrete fibrils separate from Type III collagen, and becomes restricted to the margins of bone cells and the bone surface by 7 years. The distribution of fibrillin resembles that of Type III collagen in the fetus, but at 7 years is absent from the interior of the cortex except for the canaliculi and cement lines, and remains concentrated in discrete fibers at the bone surface.