Low-grade chronic inflammation, reflected in elevated levels of serum C-reactive protein (CRP), has recently been linked to obesity, insulin resistance syndromes such as polycystic ovary syndrome (PCOS), and an increased risk of cardiovascular disease. Because the insulin sensitizer metformin has been shown to improve metabolic disturbances in PCOS, it was of particular interest to examine serum CRP levels during metformin therapy. Twenty nonobese women [body mass index (BMI) ≤ 25 kg/m²] and 32 obese women (BMI ≥ 27 kg/m²) with PCOS were randomized to receive either metformin (500 mg twice daily for 3 months, then 1000 mg twice daily for 3 months) or ethinyl estradiol (35 μg)-cyproterone acetate (2 mg) oral contraceptive pills. The serum concentrations of CRP were significantly higher in obese than in nonobese subjects at baseline [4.08 ± 0.53 (se) vs. 1.31 ± 0.28 mg/liter; P < 0.001] and correlated to BMI and to a lesser extent waist-hip ratio, suggesting that the elevated CRP levels may be related to obesity and not only to PCOS itself. During metformin treatment, serum CRP levels decreased significantly from 3.08 ± 0.7 mg/liter to 1.52 ± 0.26 mg/liter at 6 months in the whole study population (P = 0.006) and especially in obese subjects. In contrast, the treatment with ethinyl estradiol-cyproterone acetate increased serum CRP levels from 2.91 ± 0.68 mg/liter to 4.58 ± 0.84 mg/liter (P < 0.001). Whether this effect is related to estrogen action in the liver or whether it reflects increased inflammation process and possible risks for cardiovascular disease remains unclear. The decrease of serum CRP levels during metformin therapy is in accordance with the known beneficial metabolic effects of this drug and suggests that CRP or other inflammation parameters could be used as markers of treatment efficiency in women with PCOS.