A double-blind cross-over randomized study was performed in 10 selected adult overweight and obese (body mass index greater than 27) women who had been adapted to low-energy intake for a long period of time and who had shown difficulty in losing weight with conventional hypocaloric treatment. Combined with diet therapy (1000-1400 kcal/day), l(-)ephedrine hydrochloride (50 mg three times a day per os) or placebo were administered daily before each meal, after a period of stabilization with diet only for 1 month. Each pharmacological treatment lasted for 2 months. Weight loss was significantly (P less than 0.05) greater during the ephedrine period (2.41 +/- 0.61 kg) than during the placebo period (0.64 +/- 0.50 kg). None of the patients presented clinically important side-effects. These preliminary results seem to suggest a possible role for a thermogenic compound such as ephedrine in promoting weight loss in low-energy-adapted obese women.