BACKGROUND AND OBJECTIVE: Oleoyl-estrone administration in rats results in loss of body fat and sparing protein via decreasing food intake and maintaining energy expenditure. Oleoyl-estrone also decreases insulin resistance and hyperlipidemia and has no direct estrogenic effects. Our objective was to determine whether oral oleoyl-estrone was effective in the treatment of morbid obesity in a voluntary patient. PATIENT AND METHOD: Oleoyl-estrone (150-300 mol/d) was given to a morbid obese man (BMI: 51.9) over 10 consecutive 21-day trial periods of oral drug intake followed by at least two months of recovery. This treatment was given without additional dietary restrictions. Plasma metabolites, hormones and enzymes were measured before treatment, during active administration and at recovery periods. RESULTS: Oleoyl-estrone decreased the body weight (38.5 kg in 27 months, final BMI: 40.5). No rebound trends were observed. No significant changes in blood parameters, plasma metabolites, hormones or enzymes were observed as a consequence of the treatment. CONCLUSIONS: Oleoyl-estrone decreased body weight in this subject without affecting metabolites or hormones, similarly to its effects in animal models. This means that oleoyl-estrone could have a marked potential as an anti-obesity drug.