We report the isolation of a genomic clone containing the apolipoprotein CII (apo CII) gene and 5′ and 3′ flanking sequences. A detailed restriction map of the gene has been constructed and DNA fragments that are unique, or low copy number sequences in the genome have been identified. One of these detects a common restriction fragment length polymorphism (RFLP) with the enzyme BglI. Marked linkage disequilibrium is observed between this RFLP and that detected with the apo CII cDNA clone, even though the two variable restriction enzyme sites are approximately 12 kb apart. However, the usefulness of the apo CII gene as a marker for linkage studies is increased by the use of both RFLPs.