The relative release in vitro of adipsin, vascular cell adhesion molecule (VCAM) 1, angiotensin 1-converting enzyme (ACE), and soluble tumor necrosis factor alpha receptor 2 (sTNFR2) by explants of human omental and subcutaneous adipose tissue as well as the nonfat cell fractions and adipocytes from morbidly obese gastric bypass women was compared with that by tissue from obese abdominoplasty patients. Release of VCAM-1 and ACE by omental adipose tissue explants was 220% and 80% greater, respectively, over 48 hours of incubation than that by subcutaneous adipose tissue explants. However, this difference was not seen when release by adipocytes derived from omental fat was compared with that by adipocytes from subcutaneous fat. The release of adipsin and sTNFR2 by omental adipose tissue explants did not differ from that by subcutaneous tissue adipose tissue. The release of adipsin by tissue explants over 48 hours was 100-fold greater than that of VCAM-1, ACE, or sTNFR2. Most of the release of all 4 adipokines was due to the nonfat cells because adipsin release by adipocytes was only 13% of that by the nonfat cells derived from the same amount of adipose tissue, whereas ACE release by adipocytes was 7% and release of VCAM-1 as well as sTNFR2 by adipocytes was 4% or less of that by nonfat cells. The total release in vitro of ACE and sTNFR2, but not that of adipsin or VCAM-1, was enhanced in adipose tissue explants from morbidly obese women as compared with those by explants derived from obese women. We conclude that although human adipose tissue explants release appreciable amounts of adipsin and far smaller amounts of VCAM-1, ACE, and sTNFR2 in vitro, more than 87% of the release is due to the nonfat cells present in adipose tissue. Furthermore, the enhanced release of VCAM-1 and ACE seen in omental adipose tissue explants as compared with explants of subcutaneous adipose tissue is due to release by nonfat cells.