Objective: To determine whether a mutation in the GnRH receptor gene is responsible for polycystic ovary syndrome (PCOS). Design: Molecular analysis of human genomic DNA. Setting: Academic research environment. Patient(s): Eighty patients with PCOS. Intervention(s): Extraction and polymerase chain reaction (PCR) analysis of genomic DNA, confirmation of PCR products by ethidium bromide staining of agarose gels after electrophoresis, denaturing gradient gel electrophoresis of PCR products, and photography. Main Outcome Measure(s): Mutations in the GnRH receptor of women with PCOS. Result(s): Denaturing gradient gel electrophoresis revealed no mutations in the exonic sequence encoding the open reading frame of the GnRH receptor. Conclusion(s): A mutation in the GnRH receptor gene is unlikely to be the underlying cause of PCOS in most patients. The molecular basis of this disorder remains unknown.