Abstract: Our studies involved 21 women of Caucasian descent with PCOS, as diagnosed by ultrasound, clinical and hormonal findings. We determined 17a-OHP, 21-DOF and cortisol levels both just before and one hour after intravenous ACTH administration (0.25 mg Synacthen) in addition to the basal plasma levels of DHEA-S and free testosterone. We screened the CYP21 gene for 12 common-point mutations, finding five heterozygous mutations in 4 out of 21 cases (19%): a splice-site mutation in intron 2 in three cases, and a I172N mutation in exon 4 in two cases. These patients also displayed significantly higher 21-DOF or 17a-OHP plasma levels after ACTH administration, suggesting a partial 21-hydroxylase deficiency. Furthermore, we found the basal plasma DHEA-S levels or DHEA-S/F ratios in 11 of 21 patients (52%) to be higher than the means + 2SD of control females, indicating partial 3b-HSD deficiency or 17,20-LHA. According to the literature, mutations could not be found in the genes of PCO cases with hormonal activity changes in the last two enzymes. The DDT metabolite o,p-DDD is a strong inhibitor of 3b-HSD, and DDT can induce 17,20-LHA, implying a possible connection between cases of PCOS women born in East Germany after 1955 and their prenatal DDT uptake. The approximately fourfold higher prevalence of PCO and significantly increased frequency of 3b-HSD-deficiency and 17,20-LHA found in women with PCOS born since 1955the time of massive application of DDTgive weight to the thesis that DDT, rather than genetic factors, has played a part in this upsurge.