The thermogenic effect of a single oral dose of ephedrine (1 mg/kg body weight) was studied by indirect calorimetry in five women with 14% overweight before, during and 2 mo after 3 mo of chronic ephedrine treatment (20 mg, perorally, three times daily). Before treatment and 2 mo after its cessation a similar thermogenic response to ephedrine was observed. The total extra consumption of oxygen was 1.3 1 before and 1.2 1 after cessation of the chronic treatment. After 4 and 12 wk of treatment ephedrine elicited a more sustained response, the extra oxygen consumption in the 3 h following ephedrine intake being 7.0 and 6.9 1, respectively. The ratio of serum T3 to T4 increased significantly after 4 wk of treatment (15.6 +/- 1.3 vs 19.4 +/- 2.4; p less than 0.05), but decreased below the initial value after 12 wk treatment. The mean body weight was significantly reduced after 4 and 12 wk of treatment (2.5 and 5.5 kg, respectively). An improved capacity for beta-adrenergic induced thermogenesis may be useful in the treatment of obesity.