The major proteoglycan of pig skin, a proteodermatan sulfate, has been isolated under mild conditions in the presence of protease inhibitors. After purification by ion exchange and gel chromatography, it has a Mr of 70 x 10(3) and it does not form aggregates with hyaluronic acid. It contains about 60% protein, one chain of dermatan sulfate, and several oligosaccharide chains. The dermatan sulfate is high in iduronic acid (85% of the uronic acid) and there are no chains of chondroitin sulfate present. The oligosaccharides contain glucosamine, sialic acid, and neutral sugars.