B-Endorphin (B-Ep), ACTH and cortisol circulating levels, before and after a two months therapy with a hypocaloric diet and an increase in physical exercise, were measured by RIA in 17 obese female subjects. After therapy, the body weight excess fell from 56.6 +/- 22.2% to 38.6 +/- 22.1% (p less than 0.01). Plasma levels of B-Ep decreased from 18.3 +/- 12.5 fmol/ml to 6.4 +/- 3.5 fmol/ml (p less than 0.01); those of ACTH from 46.8 +/- 22.8 pg/ml to 31.2 +/- 11.6 pg/ml (p less than 0.01); and those of cortisol from 15.9 +/- 4.6 micrograms% to 10.3 +/- 2.5 micrograms% (p less than 0.01). The reduction of the elevated plasma B-Ep levels found in obese subjects is related principally to the diet therapy. Thus, as shown in experimental animals, excessive feeding results in an increased hypothalamic-pituitary secretion of B-Ep.