An apolipoprotein A-I gene promoter polymorphism, due to an adenine (A) to guanine (G) transition 78 base pairs upstream from the transcription initiation site, was studied by amplification of the corresponding region of the apoA-I gene, DNA sequencing, and allele-specific oligonucleotide hybridization. The frequency of the polymorphism was studied on female and male individuals classified into three groups according to the high density lipoprotein (HDL) cholesterol concentration. The allelic frequencies for the A polymorphism were 0.10, 0.14, 0.27 in women and 0.08, 0.17, 0.14 in men in the lowest, in the intermediate (between 10th and 90th percentile), and the highest decile of HDL cholesterol levels, respectively. Statistical analysis showed a significant difference of allelic frequencies between the highest and the lowest deciles (P less than 0.006) and between the highest and the intermediate deciles of HDL cholesterol in women (P less than 0.04) but not in men. As the sequences surrounding the polymorphism are known to be involved in transcription modulation, it is possible that the A-G transition polymorphism may have an influence on apoA-I synthesis and, in consequence, on the HDL cholesterol levels in women.