DES (Diethylstilbestrol) was used for the treatment of corpus luteum insufficiences in early pregnancy. Prenatal exposure to DES leads to an increased frequency of vaginal cancer in female offspring. DES causes persistent alterations of steroid hormone binding in the vaginal tissue. The frequency of a polymorphism (PROGINS) of human progesterone receptor (hPR) gene which is associated with an increased risk of sporadic ovarian cancer was tested in DES-exposed offspring with vaginal dysplasia. Genomic DNA was isolated from the serum of 15 US Caucasian DES-offspring. PROGINS analysis was performed using sequencing, gel-electrophoresis and SSCP-PCR. The results demonstrated that the frequency of PROGINS is increased in DES-offspring (DES: 6.7% homozygous, 26.7% heterozygous, normal US Caucasians: 3.3% homozygous, 15% heterozygous). Mutation screening of PROGINS is an important advantage for the clinical management of screening and can give additional information to prevent or find vaginal cancer in early stages in DES-offspring.