Objective: To test the hypothesis that adrenal androgen (AA) secretion is an inherited trait in PCOS and that serum DHEAS concentrations, as a marker of AA secretion, will be correlated between women with PCOS and their sisters. Design: Prospective case-control. Setting: Tertiary care center. Patient(s): Sixty-two PCOS probands and 69 sisters. Intervention(s): None. Main Outcome Measure(s): The DHEAS concentrations and clinical phenotypes were obtained. Familial correlation between sisters was estimated. A variance components model was used to estimate the heritability (h2) of the DHEAS levels. Body mass index (BMI)-adjusted DHEAS levels were used in all of the analyses. Result(s): There was no difference in age between the proband and sister groups (28.7 ± 8.1 years vs. 28.0 ± 8.8 years, P=.65), and probands had higher BMI values (33.4 ± 7.6 kg/m2 vs. 27.9 ± 7.0 kg/m2, P<.001). Sixteen of the 69 (23.2%) sisters were affected by PCOS. The sister-sister correlation of DHEAS level was 0.28 ± 0.12 for the whole group (P<.05), and this correlation was higher, at 0.38 ± 0.14 (P≤.05), after excluding 31% of the affected sisters and 34% of the unaffected sisters who received hormonal therapy at or within 3 months of the time of the study. The h2 estimates of DHEAS were 0.43 (P=.037) and 0.44 (P=.062) when all sisters and only untreated sisters, respectively, were included in the analysis. Conclusion(s): The correlation of serum DHEAS levels between PCOS probands and their sisters suggests a familial component in the regulation of DHEAS levels and possibly AA production in PCOS. The h2 estimates of 0.43-0.44 for BMI-adjusted DHEAS suggest that genetic factors account for between 40% and 50% of the overall variation in DHEAS levels in these women. Our results support the hypothesis that circulating AA levels represent an inherited trait in PCOS. © 2006 American Society for Reproductive Medicine.