OBJECTIVE: To assess the association of polymorphisms in the aromatase gene (CYP19) and on the Y-chromosome, with adult height and insulin resistance in a UK Caucasian population, after a recent report indicated these variants explain 4 cm of adult male height variation. PATIENTS AND DESIGN: We performed an association study using 917 healthy UK Caucasian subjects from the Exeter Family Study, an ongoing consecutive-birth cohort. Our study had > 85% (95% for the CYP19 variant; 85% for the Y variant) power to detect the association suggested by the previous study. MEASUREMENTS: Subjects'CYP19 genotype were determined using tetra-primer PCR, and the Y-chromosome variant genotype was identified using a restriction fragment length polymorphism (RFLP) method. Trained research nurses were responsible for measurement of height. Fasting insulin concentration was determined by an immunoenzymometric assay. RESULTS: We did not find any evidence for an effect of the CYP19 polymorphism or Y-RFLP on adult height (P > 0.83 for both variants). In addition, there was no evidence for an effect on insulin resistance in a subset of 416 subjects (P > 0.46). CONCLUSION: We have not confirmed the initial observation in a larger replication cohort. Our results highlight the importance of replicating initial results from genetic association studies.