CYP2J subfamily cytochromes P450 catalyze the NADPH-dependent oxidation of arachidonic acid to several unique eicosanoids that possess numerous biological activities including modulation of ion transport, control of bronchial and vascular smooth muscle tone, and stimulation of peptide hormone secretion. We have identified sequence variants in the 3' untranslated regions of two mouse Cyp2j genes (Cyp2j5 and Cyp2j6) and used a PCR-based oligonucleotide hybridization assay to map both genes to the central region of chromosome 4 distal to the Jun oncogene. The corresponding human CYP2J gene (CYP2J2) has been assigned to human chromosome 1 on a panel of somatic hybrid cell lines and to 1p31.3-p31.2 by fluorescence in situ hybridization analysis. The proximity of the Cyp2j cluster to the Cyp4a cluster suggests that these genes may be part of a cassette of P450 genes involved in the oxidation of fatty acids.