Inflammation and insulin resistance are often present in Polycystic Ovary Syndrome (PCOS).We determined the effect of saturated fat ingestion on mononuclear cell (MNC) nuclear factor-B (NFB) activation, NFB, inhibitory-B (IB) and TNF gene expression, and circulating C-reactive protein (CRP) in women with PCOS.Cross-sectional study.Academic medical center.Twenty reproductive-age women with PCOS (10 lean, 10 with obesity) and 20 ovulatory controls (10 lean, 10 with obesity).Activated NFB, NFB heterodimer subunits, IB and TNF mRNA content and NFB p65 and IB protein content were quantified in MNC, and CRP was measured in plasma from blood drawn fasting and 2, 3 and 5 hours after saturated fat ingestion. Insulin sensitivity was derived from oral glucose tolerance testing (ISOGTT). Androgen secretion was assessed from blood drawn fasting and 24, 48 and 72 hours after HCG administration.In response to saturated fat ingestion, women with PCOS regardless of weight class exhibited lipid-induced increases in activated NFB, NFB and TNF gene expression and plasma CRP, and decreases in IB protein compared with lean control subjects. Both PCOS groups exhibited lower ISOGTT and greater HCG-stimulated androgen secretion compared with control subjects. Lipid-stimulated NFB activation was negatively correlated with ISOGTT, and positively correlated with HCG-stimulated androgen secretion.In PCOS, increases in NFB activation and circulating CRP and decreases in IB protein following saturated fat ingestion are independent of obesity. Circulating MNC and excess adipose tissue are separate and distinct contributors to inflammation in this disorder.