The present studies examined the effect of obesity in humans on the release of transforming growth factor beta1 (TGF-beta1) by human adipose tissue. The regulation of TGF-beta1 release by adipose tissue as well as the question of whether its release is due to the adipocytes or the nonfat cells in adipose tissue was also examined. There was a statistically significant (r=0.50) correlation between the body mass index of the fat donors and the subsequent release of TGF-beta1 release by subcutaneous adipose tissue. There was also a positive correlation between total TGF-beta1 release by adipose tissue explants and body fat content (r=0.69). The question of whether tumor necrosis factor alpha (TNF-alpha) and/or interleukin 1 beta (IL-1 beta) regulate the release of TGF-beta1 was investigated by incubation of adipose tissue explants with a soluble human TNF-alpha receptor (etanercept) and a neutralizing antihuman IL-1 beta antibody. The release of TGF-beta1 over 48 hours by adipose tissue explants was significantly enhanced in the presence of both the inhibitor of TNF-alpha and of IL-1 beta. It is of interest, in view of the elevated circulating insulin in blood of morbidly obese women, that the release of TGF-beta1 by adipose tissue was enhanced in the presence of insulin. The question of whether the release of TGF-beta1 by human adipose tissue explants was primarily due to adipocytes, as is the case for leptin, or the nonfat cells present in human adipose tissue, as is the case for IL-8 and prostaglandin E(2), was examined. The release of TGF-beta1 was primarily by the nonfat cells of human adipose tissue because release by adipocytes was less than 10% of that by the nonfat cells of adipose tissue.