Rat CYP2A3 and mouse CYP2A5 are predominantly expressed in the olfactory mucosa. CYP2A3 is also expressed in the lung at a low level, whereas CYP2A5 is expressed in several additional tissues. To better understand the transcriptional regulation of the CYP2A genes, transgenic mice were generated with a full-length CYP2A3 gene fragment containing 3.4 kilobases of the 5'-flanking region. CYP2A3 mRNA was detected in the brain and olfactory bulb in four transgenic mouse lines, in the olfactory mucosa in three lines, and in kidney, liver, lung, and small intestine in two lines. Thus, the expression of the CYP2A3 transgene mimicked the tissue distribution pattern of mouse CYP2A5 rather than that of rat CYP2A3. Furthermore, the levels of CYP2A3 mRNA were very low in all lines examined, suggesting that more distal regulatory regions may be involved in the abundant expression of the CYP2A genes in the olfactory mucosa.