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.