In a method of isolating osteogenic protein from bone, in which an osteogenic protein-containing fraction is extracted from bone and enriched by a sequence of enrichment steps selected from ultrafiltration and chromatography, the invention provides the improvement of removing higher molecular weight components from the osteogenic protein-containing fraction prior to the enrichment steps. The higher molecular weight components have a molecular weight of about 100-300 kDa and are selected from collagen, collagen fragments, collagen aggregates and mixtures thereof.