When given as a supplement to an energy restricted diet the sympathomimetic agent ephedrine, in combination with methylxanthines such as caffeine, improves fat loss by dual actions: a central suppression of appetite and peripheral stimulation of energy expenditure covered by fat oxidation, Mean weight loss was found to be 16.6 kg after 6 months when E+C was given as an adjuvant to an efficient hypoenergetic diet, which was 3,4 kg higher than in the placebo group, An additional 24 weeks treatment with E+C prevented relapse,In the first weeks of treatment E+C offset the hypotensive effect of energy restriction and weight loss, but the effect was transient, and after 8 weeks blood pressures were indistinguishable from those of the placebo group, E+C has no adverse effect on glucose and lipid metabolism, but has been shown to prevent the decline in HDL-cholesterol caused by weight loss, In a comparative trial the weight loss produced by E+C was similar to that of dexfenfluramine. More research on sympathomimetics and methylxanthines should he carried out to identify combinations with imp roved efficiency and safety, Moreover, more long-term trials and studies in males are required.