Abstract: Thrombospondin-binding molecules and fragments comprising one or more regions of the TSP-1-binding domains of Histidine-Rich Glycoprotein (HRGP) are provided. Also provided are homologs of TSP-1-binding domains of Histidine-Rich Glycoprotein. Therapeutic methods of use of these thrombospondin-binding molecules and fragments, as well as anti-HRGP antibodies and antibody fragments are disclosed. These methods are useful in modulating a variety of physiological and pathological processes including angiogenesis, inflammatory responses, embryogenesis and tumor proliferation. A range of assay methods for diagnosis and for detection, quantitation and identification of modulators of the TSP-l-binding activity of HRGP are also provided. In addition screening assays for compounds that specifically modulate HRGP expression are provided. These assays are useful in a range of formats from individual assays to library screening as well as high throughput assays.