The CYP2C gene cluster on chromosome 10q24 encodes the P450IIC enzymes, members of the cytochrome P450 monooxygenase superfamily. The P450-IIC enzymes are required for the metabolism of a number of foreign compounds, including the drugs mephenytoin and tolbutamide, and are also thought to be involved in the metabolism of endogenous steroid hormones. Several different CYP2C cDNA clones have been isolated; however, the exact number of genes and the genomic arrangement of the CYP2C cluster have remained unknown. Using a combination of STS and restriction mapping to characterize YAC clones, we have constructed a 2.4-Mb physical map that incorporates the CYP2C gene cluster. The cluster spans approximately 500 kb on proximal 10q24 and comprises four genes arranged in the order CYP2C8-CYP2C9-CYP2C19-CYP2C18. The map also includes an adjacent gene, the serum retinol binding protein gene (RBP4). The incorporation of Généthon CA repeat genetic markers suggests the orientation of the loci to be Cen-RBP4-CYP2C18-CYP2C19-CYP2C9-CYP2C8-Tel .