To evaluate the effect of weight loss and diet therapy on plasma sex hormone behavior in male obesity, 9 men with a BMI of 43.4 +/- 6.3 participated in an 8-week semistarvation program [whose energy content ranged from 320 to 500 k calorie/day (proteins 44 to 60 g and carbohydrates 54 to 81 g per day)] followed by a two-week hypocaloric (1000 k calorie/day) refeeding. In basal conditions, obese patients presented higher estrogen and lower dehydroepiandrosterone sulphate, testosterone (total and free) and sex-hormone binding globulin concentrations with respect to a group of control normal-weight subjects. Cumulative weight loss was 23.9 +/- 3.6 kg after semistarvation and 24.4 +/- 4.8 kg after refeeding (p = NS). A significant increase in testosterone, free testosterone and dehydroepiandrosterone sulfate was observed throughout the study, irrespective of dietary intake. A transient increase occurred in estrone levels while 17B-estradiol did not change. Gonadotropins and sex-hormone binding globulin values remained unaltered. No relationship was found between sex hormones and dietary energy content or composition. Daily urine free cortisol, which was used as a parameter of adrenal function, fell approximately 50% during semistarvation but returned to baseline values after refeeding. These results show that in massively obese patients weight loss per se may partially reverse sex hormone abnormalities but not sex-hormone binding globulin concentrations. It remains to be determined whether the return to "normal weight" can normalize steroid metabolic derangements in the obese man.