Objective: Hyperinsulinemia is a prevalent feature of polycystic ovary syndrome (PCOS), contributing to metabolic and reproductive manifestations of the syndrome. Weight loss reduces hyperinsulinemia but weight regain is the norm, thus preventing long-term benefits. In the absence of weight loss, replacement of dietary carbohydrate (CHO) with mono/polyunsaturated fat reduces ambient insulin concentrations in non-PCOS subjects. The current study evaluated whether this dietary intervention could ameliorate hyperinsulinemia in women with PCOS.Design/setting/patients: Obese women with PCOS (BMI 397kg/m(2)) and insulin resistance completed a crossover study (Stanford University Clinical Research Center) comparing two isocaloric diets, prepared by research dietitians, containing 60% CHO/25% fat versus 40% CHO/45% fat (both 15% protein and 7% saturated fat). After 3 weeks on each diet, daylong glucose, insulin, and fasting lipid/lipoproteins were measured.Results: Daylong glucose did not differ according to diet. Daylong insulin concentrations were substantially (30%) and significantly lower on the low CHO/higher fat diet. Beneficial changes in lipid profile were also observed.Conclusions: Replacement of dietary CHO with mono/polyunsaturated fat yields clinically important reductions in daylong insulin concentrations, without adversely affecting lipid profile in obese, insulin-resistant women with PCOS. This simple and safe dietary intervention may constitute an important treatment for PCOS.ClinicalTrials.gov Identifier: NCT00186459