17 patients with refractory obesity, who had gained an average of 0.7 +/- 1.9 kg during 12 weeks treatment with diet and placebo, lost a mean of 2.9 +/- 0.5 kg after 12 weeks sequential treatment with dexfenfluramine 15 mg twice daily (p less than 0.001). In a second trial, 29 patients were treated for 24 weeks with dexfenfluramine; average cumulative weight loss after 12 weeks in these patients (5.7 +/- 0.1 kg) was significantly greater than in the patients who had been treated initially with placebo. After 24 weeks of dexfenfluramine treatment there was a further significant increase in cumulative weight loss (7.0 +/- 0.8 kg; p = 0.05). The incidence of side effects in both trials was lower than that reported in previous studies of racemic dlfenfluramine. The clinically significant weight loss, and low incidence of unwanted effects, suggest that dexfenfluramine has a role in the treatment of refractory obesity.