A study was carried out in 6 healthy volunteers to test the hypothesis that weight gain associated with amitriptyline treatment may be due to hypoglycaemia caused by increased circulating blood insulin. Subjects were treated with 50 mg amitriptyline b.d. for 28 days. Estimations made of serum levels of amitriptyline and its metabolite nortriptyline showed a steady state by the 10th day. No significant weight-gain was observed in any of the volunteers, although 2 reported an increase in appetite. There were no significant differences in any of the glucose tolerance curves, fasting or peak insulin levels or in the glucose/insulin curves for Days 0, 14 and 28.