Objective: To obtain more information on the possible influence of body mass index (BMI) and weight loss on interleukin-8 (IL-8) in plasma and in the adipose tissue. Tumor necrosis factor-alpha (TNF-alpha) was used for comparison and determined in parallel with IL-8. Research Methods and Procedures: The study was divided into three parts: 1) a cross-sectional study that included 89 subjects; 2) a 20-week intervention study in which 34 healthy obese subjects received a dietary intervention for 8 weeks followed by an additional 12 weeks on a weight-stabilization diet; 3) from this latter study, a subgroup of 8 obese subjects was investigated with a subcutaneous adipose-tissue biopsy. Results: In the cross-sectional study, plasma levels of TNF-alpha (p < 0.01), but not IL-8, was correlated with BMI. However, in a subgroup (BMI, 20 to 30 kg/m(2)), IL-8 was correlated with BMI (p < 0.01). In the intervention study, weight loss and weight maintenance led to an increase in IL-8 by 30% (p < 0.05) and a decrease in TNF-alpha by 40% (p < 0.001), which were paralleled in the adipose tissue, demonstrating a 2- to 3-fold increase (p < 0.01) and a 40% to 80% decrease (p < 0.01) in IL-8 and TNF-alpha, respectively. Discussion: Weight loss in obese subjects was associated with opposite changes in the secretion and transcription of IL-8 and TNF-alpha in the adipose tissue, as well as in plasma. This could indicate that plasma IL-8 under some conditions may be related to changes in adipose tissue IL-8 production.