CYP2G1is an abundant, olfactory mucosa-specific cytochrome P450 enzyme active in the metabolism of sex steroids and xenobiotic substrates in mammalian animals. Two different humanCYP2Ggenes,CYP2GP1andCYP2GP2, were characterized in the present study. Polymorphisms in these genes were also studied.CYP2GP1contained a single nucleotide deletion in exon 2 (ΔC) and a 2.4-kb deletion between exons 3 and 7 (ΔE4–6), whereasCYP2GP2contained a nonsense mutation in exon 1 and another in exon 3. The coding region sequences in exons 1–3 and 7–9 of the two genes were 96.7% identical. Both genes were localized to human chromosome 19, and Southern blot analysis of human genomic DNA did not detect any additional copies of theCYP2Ggene. The occurrence of these loss-of-function mutations was analysed by polymerase chain reaction-based genotyping in more than 200 individuals. The ΔE4–6 deletion inCYP2GP1was detected in 94% of subjects (either homozygous or heterozygous), and an allele which does not contain this deletion was detected in 11.6% of individuals. The nonsense mutation inCYP2GP2exon 3 was detected in 86% of individuals (either homozygous or heterozygous); however, a potentially functionalCYP2GP2allele based on the absence of the nonsense mutation in exon 3 was also detected in 31% of individuals. These results indicate that a functionalCYP2Gallele is rare in humans. Analysis of the allelic distribution in different ethnic groups suggested that a functionalCYP2Gallele, if present, is more likely to be found in Black and Hispanic subjects.