There is some evidence that blockade of alpha 2-adrenoceptors on adipocytes may lead to an increase in lipolysis, We have therefore carried out a double blind comparative study of the effects of the selective alpha 2-antagonist yohimbine in human obesity. Nineteen obese volunteers participated in the study. Subjects were randomly allocated to the yohimbine group (n = 10, 18 mg yohimbine/day), or to the placebo group (n = 9). All subject were maintained on a hypocaloric diet (1000 kcal/day) during the 8 weeks of the study. There was no difference between the two groups with respect to either body weight, blood pressure supine and erect or heart rate during the different phases of the study. We found no difference in the lipid parameters (triglycerides, cholesterol, glycerol, beta-OH-butyrate, acetoacetate and free fatty acids) between the two groups. These results suggest that at the dose used the yohimbine does not influence the function of the alpha 2-adrenoceptors on the adipocytes; does not increase the lipolysis and does not represent an effective treatment of obesity.