The prospective, cross-sectional study was undertaken to evaluate the relation between the fat mass and serum leptin level in patients with rheumatoid arthritis (RA). Low body mass and anorexia are commonly found in patients with RA. Inflammatory cytokines may significantly influence the secretion of anorectic hormone--leptin--that was confirmed in both experimental and clinical studies. Fifty-two non-diabetic and non-obese patients (38 females, 14 males) were studied. Mean age was 56 +/- 11 years and mean body mass index (BMI) 24.6 +/- 4.1 kg/m2. The disease activity score (DAS) was 3.9 +/- 1.4; range 1.4-7.4, and disease duration 8.1 +/- 6.7 years. Serum leptin was measured by ELISA and body composition by double X-ray densitometry. Mean serum leptin concentration was 2.8 +/- 1.4 ng/ml in patients with RA was lower than in the control group (4.2 +/- 2.0). In a simple regression analysis leptin did not correlate with BMI (R Spearman = 0.01), C-reactive protein (R = 0.08), total fat mass (R = 0.08), trunk fat (R = 0.05), limbs fat (R = 0.09) and DAS (R = -0.17). This relation was also not influenced by gender or type of immunosuppressive therapy. In a multiple regression model none of the independent variables explained the significant portion of variance of serum leptin. It is concluded that the physiologic relation of serum leptin to body fat stores is not present in patients with RA.