To clone novel brain proteoglycans, we employed a strategy based on polyclonal antisera that recognize multiple proteoglycan core proteins. By using an antiserum raised against a fraction enriched for proteoglycans, we isolated three groups of cDNAs from a bovine brain lambda gt11 library. One of the cDNA groups has been fully sequenced and shown to encode a novel proteoglycan core protein of the aggrecan/versican family. This proteoglycan, named brevican, carries chondroitin sulfate chains, and, like other members of the family, contains a hyaluronic acid-binding domain in its N-terminal region, an epidermal growth factor-like repeat, a lectin-like and a complement regulatory protein-like domains in its C-terminal region. In contrast, the central region of brevican is much shorter than that of aggrecan, versican, or neurocan, and shows little homology with these proteoglycans. Brevican core protein exists as a 145 kDa full-length form and a 80 kDa N terminally truncated form. A significant amount of brevican devoid of any glycosaminoglycan chains is present in the brain, indicating that brevican is a "part-time" proteoglycan. Northern blot analysis reveals that a single 3.3-kilobase brevican transcript is present predominantly in the brain, and that it is expressed in primary cerebellar astrocytes but not in neurons.