The present studies were designed to compare the relative release of interleukin 1 receptor antagonist (IL-1Ra), cathepsin S, macrophage migration inhibitory factor (MIF), nerve growth factor (NGF), and interleukin 18 (IL-18) by adipocytes as compared with the non-fat cells present in subcutaneous and omental adipose tissue from morbidly obese gastric bypass patients as compared with obese abdominoplasty patients. The release of IL-1Ra, cathepsin S, and MIF by explants of human adipose tissue incubated for 48 hours averaged 6, 9, and 19 pmol/g, respectively, and was far greater than the release of NGF (0.05 pmol/g) or IL-18 (0.006 pmol/g). The release by human adipocytes of IL-1Ra, cathepsin S, and MIF was 0.13, 0.32, and 2.6 pmol/g, respectively, over 48 hours, whereas NGF release was 0.003 and IL-18 0.001 pmol/g. Only the total release of MIF by human adipose tissue explants was enhanced, whereas that of IL-18 was significantly reduced in explants from morbidly obese women. Most of (55%-73%) the release of IL-1Ra, cathepsin S, MIF, NGF, and IL-18 was by the adipose tissue matrix, whereas release by stromal-vascular (SV) cells was 3% to 28% of total release over 48 hours by the adipose tissue matrix, SV cells and adipocytes. The release of NGF by adipocytes was 42%, that of MIF was 27%, and for the other factors 15% or less of release over 48 hours by the adipose tissue matrix, SV cells, and adipocytes. Our results suggest that the non-fat cells in human adipose tissue contribute to most of the release of NGF, IL-18, IL-1Ra, cathepsin S, and MIF seen during primary culture of adipose tissue explants from obese women.